Diabetes

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.

The dramatically positive safety and efficacy results from the DAPA-CKD trial, which showed that treatment with the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin significantly cut both chronic kidney disease progression and all-cause death in patients with or without type 2 diabetes, were also notable for broadening the population of patients eligible for this treatment to those in the upper range of stage 4 CKD.

Courtesy European Society of Cardiology

Of the 4,304 CKD patients enrolled in DAPA-CKD, 624 (14%) had an estimated glomerular filtration rate (eGFR) of 25-29 mL/min per 1.73m², an unprecedented population to receive a drug from the SGLT2 inhibitor class in a reported study. The results provided definitive evidence for efficacy and safety in this range of renal function, said Hiddo J.L. Heerspink, Ph.D., at the virtual annual meeting of the European Association for the Study of Diabetes.

Until now, the widely accepted lowest level for starting an SGLT2 inhibitor in routine practice has been an eGFR as low as 30 mL/min per 1.73 m².
 

Using SGLT2 inhibitors when eGFR is as low as 25

“It’s time to reduce the eGFR level for initiating an SGLT2 inhibitor to as low as 25,” said Dr. Heerspink, a professor of clinical pharmacology at the University of Groningen (the Netherlands).

While conceding that this is primarily a decision to be made by guideline writers and regulatory bodies, he declared what he believed was established by the DAPA-CKD findings: “We’ve shown that dapagliflozin can be safely used in these patients. It is effective across the spectrum of kidney function.”

Other experts not associated with the study agreed.

Sara Freeman/MDedge News

The trial researchers were “brave” to enroll patients with eGFRs as low as 25 mL/min per 1.73 m², and “we urgently need these agents in patients with an eGFR this low,” commented Chantal Mathieu, MD, an endocrinologist and professor of medicine at Catholic University in Leuven, Belgium, and designated discussant for the report. Overall, she called the findings “spectacular,” a “landmark trial,” and a “winner.”

The study also set an new, lower floor for the level of albuminuria that can be usefully treated with dapagliflozin (Farxiga) by enrolling patients with a urinary albumin-to-creatinine ratio as low as 200 mg/g; the previous lower limit had been 300 mg/g, noted Dr. Mathieu. The new findings pose challenges to guideline writers, regulators who approve drug labels, and payers to a quickly make changes that will bring dapagliflozin to a wider number of patients with CKD.

Once the full DAPA-CKD results are reported, “it will change practice, and push the eGFR needle down” to as low as 25. It will also lower the albuminuria threshold for using dapagliflozin or other drugs in the class, commented David Z.I. Cherney, MD, a nephrologist at the University of Toronto. “It’s just one study,” he admitted, but the consistent renal benefits seen across several studies involving all four drugs in the SGLT2 inhibitor class will help hasten this change in identifying treatable patients, as well as expand the drug class to patients with CKD but no type 2 diabetes (T2D).

“I don’t think we’ve ever had stronger evidence” for drugs that can benefit both heart and renal function, plus the drug class is “very safe, and really easy to start” and maintain in patients, Dr. Cherney said in an interview. “It’s wonderful for these patients that we now have something new for treatment,” a drug with a “very favorable benefit-to-risk ratio.”
 

Results show many dapagliflozin benefits

While this broadening of the range of patients proven to tolerate and benefit from an SGLT2 inhibitor was an important consequence of DAPA-CKD, the study’s primary finding – that dapagliflozin was as safe and effective for slowing CKD progression in patients regardless of whether they also had T2D – will have an even bigger impact on expanding the target patient population. Showing efficacy in patients with CKD but without a T2D etiology, the status of about a third of the enrolled 4,304 patients, makes this treatment an option for “millions” of additional patients worldwide, said Dr. Heerspink. “These are the most common patients nephrologists see.” A major challenge now will be to do a better job finding patients with CKD who could benefit from dapagliflozin.

DAPA-CKD enrolled CKD patients based primarily on prespecified albuminuria and eGFR levels at more than 300 centers in 34 countries, including the United States. Virtually all patients, 97%, were on the only treatment now available with proven efficacy for slowing CKD, either an ACE inhibitor or an angiotensin receptor blocker. The small number of patients not on one of these drugs was because of poor tolerance.

The study’s primary endpoint was the combined rate of cardiovascular death, renal death, end-stage renal disease, or a drop in eGFR of at least 50% from baseline. This occurred in 14.5% of patients who received placebo and in 9.2% of those who received dapagliflozin during a median follow-up of 2.4 years, a highly significant 39% relative risk reduction. Concurrently with the report at the virtual meeting the results also appeared online in the New England Journal of Medicine. This 5.3% cut in the absolute rate of the combined, primary adverse outcome converted into a number needed to treat of 19 to prevent 1 event during 2.4 years, a “much lower” number needed to treat than reported for renin-angiotensin system inhibitors in these types of patients, Dr. Heerspink said.

Notable positive secondary outcomes included a significant 31% relative cut (a 2% absolute decline) in all-cause mortality, “a major highlight” of the findings, Dr. Heerspink said. Dapagliflozin treatment also linked with a significant 29% relative cut in the incidence of cardiovascular death or hospitalization for heart failure.

“Cardiovascular disease is the most common cause of death in patients with CKD,” explained David C. Wheeler, MD, a coinvestigator on the study and professor of kidney medicine at University College London. “The heart and kidney are intertwined. This is about cardiorenal disease.”

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin. Dr. Heerspink has been a consultant to and received research funding from AstraZeneca. He has also received personal fees from Mundipharma and Novo Nordisk, and he has also served as consultant to several other companies with the honoraria being paid to his institution. Dr. Mathieu has had relationships with AstraZeneca and several other companies. Dr. Cherney has been a consultant to and has received research funding from AstraZeneca and several other companies. Dr. Wheeler has received personal fees from AstraZeneca and from several other companies.

[email protected]

SOURCE: Heerspink HJL et al. EASD 2020 and N Engl J Med. 2020 Sep 24. doi: 10.1056/NEJMoa2024816.

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Further analyses from the cardiovascular outcome trial of the sodium-glucose transporter 2 inhibitor ertugliflozin in patients with type 2 diabetes helped better define positive effects the drug had on preserving renal function, and also gave a tantalizing hint that this drug, and hence possibly the entire SGLT2 inhibitor drug class, may benefit patients with heart failure with reduced ejection fraction.

But the underlying problem for ertugliflozin (Steglatro) – first seen when results from the VERTIS CV trial initially came out in June 2020 at the annual meeting of the American Diabetes Association – was that, while the trial met its primary endpoint of proving noninferiority to placebo for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke, treatment with ertugliflozin showed no suggestion of benefit, compared with placebo for reducing this endpoint, producing a nonsignificant 3% relative cut in the combined rate of these adverse events, compared with placebo treatment.
 

‘Somewhat disappointing’ trial performance

Overall, results from VERTIS CV with ertugliflozin were “somewhat disappointing,” commented Melanie J. Davies, MD, who was not involved with the study and chaired a session at the virtual annual meeting of the European Association for the Study of Diabetes that reviewed the main results, put them into perspective, and added a few new exploratory analyses.

Although the results from 8,246-patient VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial) put ertugliflozin in the same league as other drugs from its class for safety, “we do not see the significant benefits observed in many of the previous cardiovascular outcomes trials” for other drugs in the SGLT2 inhibitor class, specifically canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), Dr. Davies said in an interview. The upshot, for at least the time being, is that ertugliflozin “is unlikely to receive a label for any new indications,” she predicted. In contrast, the other drugs in the class have, for example, received a U.S. labeled indication to reduce cardiovascular death (empagliflozin) or major cardiovascular disease events (canagliflozin) in adults with type 2 diabetes (T2D) and cardiovascular disease, or to reduce heart failure hospitalizations (dapagliflozin).

The main results from VERTIS CV, posted online in the New England Journal of Medicine after the EASD session, showed a single significant outcome difference between treatment with ertugliflozin and placebo over a median of 3.0 years of follow-up from among 10 reported secondary outcomes: a 30% relative reduction (a 1.1% absolute reduction) in the rate of hospitalization for heart failure, the sole criterion in the report by which ertugliflozin matched the benefits of the other SGLT2 inhibitors.

But the prespecified design of VERTIS CV called for a hierarchical sequence of secondary analyses. The statistically significant noninferiority of the primary endpoint allowed calculation of the initial secondary endpoint, a reduction in the combined rate of cardiovascular death or hospitalization for heart failure. Ertugliflozin treatment cut this outcome by a relative 12%, compared with placebo, a difference that was not significant.

This neutral finding brought to a stop further statistical testing of any of the other secondary endpoints, including impact on hospitalization for heart failure by itself. It also guaranteed that no beneficial effect inferred from the trial’s data would qualify for statistical validity, making it unlikely that ertugliflozin would gain any new label indications from these results. The drug carries a U.S. label that is limited to providing glycemic control.

Choosing among the SGLT2 inhibitors

“What we can say for sure is that there is a glycemic benefit and a heart failure hospitalization benefit” across all four of the SGLT2 inhibitors. “Beyond that, the best we can say today [about using these drugs in practice] is to follow regulatory indications and guidelines recommendations,” commented Javed Butler, MD, a cardiologist and professor and chair of medicine at the University of Mississippi Medical Center, Jackson.

“These results are going to lead to some serious discussions among the research, clinical, and regulatory communities about class effects versus drug effects, and specific trial data versus the totality of evidence,” he said in an interview.

“I think it will influence prescribing ertugliflozin, particularly in patients with established cardiovascular disease, or when the goal is to improve heart failure outcomes of reduce chronic kidney disease,” added Dr. Davies, a professor of diabetes medicine at the University of Leicester (England). “We already have positive benefits [proven for these outcomes] using other agents in the class.”

Perhaps one feature potentially in ertugliflozin’s favor is its price, and whatever impact that might have for payers or patients with inadequate coverage for their drug costs. U.S. websites show a typical retail price for ertugliflozin that is roughly 40% below the three other agents in the class, a difference that can add up to an annual cost savings of about $2,500.

A major consideration for clinicians deciding which SGLT2 inhibitor to prescribe should be “what can the patient afford,” noted Darren K. McGuire, MD, a coinvestigator for VERTIS CV, during discussion of the trial at the EASD virtual meeting.
 

New analyses show more renal-effect consistency

One surprise in the initial VERTIS CV report was in the study’s key renal outcome, a composite of renal death, need for dialysis, or a doubling of the serum creatinine level, which reflects a cut of at least a 50% in estimated glomerular filtration rate (eGFR). This composite outcome trended toward a significant benefit but fell short, producing a nominal 19% relative reduction. This combined endpoint probably “set the bar too high,” said David Z.I. Cherney, MD, a nephrologist who led the renal assessments run in the trial. He presented several exploratory analyses during the virtual EASD session that provided reassuring evidence that ertugliflozin was not an outlier among the SGLT2 inhibitors when it came to kidney benefits.

Perhaps the most compelling analysis he reported was a slight tweak to the main renal composite endpoint that substituted prevention of a 40% or greater reduction in eGFR for prevention of a 50% or greater reduction. By this somewhat lower bar for efficacy, treatment with ertugliflozin in VERTIS CV linked with a 34% relative risk reduction, compared with placebo (a roughly 1% absolute reduction) that was statistically significant, and importantly came out very close to the effect for this revised endpoint that had been seen for the other three SGLT2 inhibitor drugs.

Focusing on prevention of a 40% or greater drop in eGFR “gives a much more robust measure of renal protection,” Dr. Cherney, a clinician and researcher at the University of Toronto, said in an interview. “The key message is that renal protection is much more uniform” with the rest of the drugs in the class when looked at this way or by some of the other alternative parameters he reported. But the new renal analyses do not address disparities seen among the drugs in the class for several cardiovascular disease effects.

“The overall impression from VERTIS CV is that there was less cardiovascular disease benefit,” except for prevention of heart failure hospitalization, he said.

A teaser for HFpEF

One additional notable new finding discussed during the EASD session stemmed from the investigators ability to mine the medical records of enrolled patients for information about their heart failure history and left ventricular ejection fractions, a data set that was “unique,” compared with the other cardiovascular outcome trials for the drugs in the class, noted Francesco Cosentino, MD, another VERTIS CV coinvestigator and professor of cardiology at the Karolinska Institute in Stockholm.

Roughly a quarter of the enrolled patients had a history of heart failure, and about half of these patients had heart failure with preserved ejection fraction, about 1,000 total patients. In this subgroup treatment with ertugliflozin linked with a 30% relative reduction in hospitalization for heart failure, compared with placebo, a roughly 0.5% absolute reduction. The numbers were small and underpowered for producing convincing evidence, but it provided an intriguing hint of benefit for an unmet need that is currently undergoing further testing in studies designed to specifically explore benefit in this type of heart failure patient, said Dr. Cosentino.

VERTIS CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin. Dr. Davies has been a speaker on behalf of Merck and has had relationships with several other companies. Dr. Butler is a consultant to Merck and several other companies. Dr. McGuire has received honoraria from Merck, nonfinancial support from Pfizer, and has had relationships with several other companies. Dr. Cherney has received honoraria from Merck, nonfinancial research support from Pfizer, and has also had relationships with several other companies. Dr. Cosentino has received fees from Merck and Pfizer, and also from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novo Nordisk

[email protected]

Type 2 diabetes patients who had never used insulin showed sustained remission 10 years after bariatric surgery in a prospective study of 85 patients.

Having diabetes for less than 5 years was also predictive of achieving long-term diabetes remission, Diego Moriconi, MD, of the University of Pisa (Italy) and presenting study investigator, reported at the virtual annual meeting of the European Association for the Study of Diabetes.

“Weight loss was associated with type 2 diabetes remission 1 year after surgery, but it had no impact on the long-term relapse of diabetes,” Dr. Moriconi said.

The findings are important, commented Tina Vilsbøll, MD, DMSc, chief consultant at the Steno Diabetes Centre Copenhagen, who chaired the session. They’re important because they would help “to set the expectations for patients before they have surgery, what to expect in respect to resolution or remission of diabetes.”

If patients were taking insulin, for instance, the take home would seem to be not to expect too much in terms of remission of their diabetes, Dr. Vilsbøll said. She added: “Usually I am not a big fan of [relying on] diabetes duration, because often we know that patients with type 2 diabetes have had diabetes for a long time before they’re actually diagnosed.” However, “it seems to be very important here.”

Dr. Moriconi reported the findings of an observational study that had started in 2006 and recruited individuals about to undergo bariatric surgery for type 2 diabetes. Participants were evaluated before surgery and every 6-12 months after, undergoing various clinical and laboratory investigations, for a period of 10 years.

The majority of the recruited patients (76%) were women. Most (also 76%) had undergone gastric bypass (Roux-en-Y) surgery, and the remainder had undergone sleeve gastrectomy. Both types of surgery were equally as good at getting people into remission, as defined by the American Diabetes Association Standards of Medical Care in Diabetes, Dr. Moriconi said. As such, remission was achieved if the fasting blood glucose fell below 100 mg/dL and the hemoglobin A1c below 5.7%.

In the first year following surgery, 75% of patients had met diabetes remission criteria. This fell to 61% of patients after 5 years, and to 55% at 10 years. At each of these time points, 25% of patients had type 2 diabetes, with 14% relapsing back at 5 years and 20% at 10 years.

Dr. Moriconi pointed out some of the different characteristics of the 47 patients who had achieved diabetes remission at 10 years, compared with the 17 who had “relapsed” back to having type 2 diabetes and the 21 who had remained with type 2 diabetes.

The decrease in body mass index achieved at 10 years was no different between the three groups. However, 1 year after surgery, there had been a significantly greater drop in body in those who achieved remission, compared with those who did not (P = .04).

“Glycemic control improved with time in all the three groups after bariatric surgery, although more markedly so in the remission group,” Dr. Moriconi said.

He highlighted how none of the patients who had achieved remission had used insulin, whereas 12% of those who had relapsed and half (52%) of those who remained with type 2 diabetes had used insulin (P < .0001).

Patients who achieved remission at 1, 5, and 10 years were more likely to have had diabetes for less than 5 years than those who remained with type 2 diabetes. The average duration of diabetes was 2 years in those achieving remission versus 8 years in those who had relapsed and 13 years in those who had remained diabetic (P < .0001).

Logistic regression analysis, which adjusted for all major confounding factors such as age, sex, and type of surgery, showed that only the duration of diabetes and insulin therapy before surgery were the only predictors of long-term diabetes remission.

The study had no commercial funding. Dr. Moriconi and Dr. Vilsbøll had no conflicts of interest to disclose.

SOURCE: Moriconi D. EASD 2020, Oral presentation 120.

Type 2 diabetes patients who had never used insulin showed sustained remission 10 years after bariatric surgery in a prospective study of 85 patients.

Having diabetes for less than 5 years was also predictive of achieving long-term diabetes remission, Diego Moriconi, MD, of the University of Pisa (Italy) and presenting study investigator, reported at the virtual annual meeting of the European Association for the Study of Diabetes.

“Weight loss was associated with type 2 diabetes remission 1 year after surgery, but it had no impact on the long-term relapse of diabetes,” Dr. Moriconi said.

The findings are important, commented Tina Vilsbøll, MD, DMSc, chief consultant at the Steno Diabetes Centre Copenhagen, who chaired the session. They’re important because they would help “to set the expectations for patients before they have surgery, what to expect in respect to resolution or remission of diabetes.”

If patients were taking insulin, for instance, the take home would seem to be not to expect too much in terms of remission of their diabetes, Dr. Vilsbøll said. She added: “Usually I am not a big fan of [relying on] diabetes duration, because often we know that patients with type 2 diabetes have had diabetes for a long time before they’re actually diagnosed.” However, “it seems to be very important here.”

Dr. Moriconi reported the findings of an observational study that had started in 2006 and recruited individuals about to undergo bariatric surgery for type 2 diabetes. Participants were evaluated before surgery and every 6-12 months after, undergoing various clinical and laboratory investigations, for a period of 10 years.

The majority of the recruited patients (76%) were women. Most (also 76%) had undergone gastric bypass (Roux-en-Y) surgery, and the remainder had undergone sleeve gastrectomy. Both types of surgery were equally as good at getting people into remission, as defined by the American Diabetes Association Standards of Medical Care in Diabetes, Dr. Moriconi said. As such, remission was achieved if the fasting blood glucose fell below 100 mg/dL and the hemoglobin A1c below 5.7%.

In the first year following surgery, 75% of patients had met diabetes remission criteria. This fell to 61% of patients after 5 years, and to 55% at 10 years. At each of these time points, 25% of patients had type 2 diabetes, with 14% relapsing back at 5 years and 20% at 10 years.

Dr. Moriconi pointed out some of the different characteristics of the 47 patients who had achieved diabetes remission at 10 years, compared with the 17 who had “relapsed” back to having type 2 diabetes and the 21 who had remained with type 2 diabetes.

The decrease in body mass index achieved at 10 years was no different between the three groups. However, 1 year after surgery, there had been a significantly greater drop in body in those who achieved remission, compared with those who did not (P = .04).

“Glycemic control improved with time in all the three groups after bariatric surgery, although more markedly so in the remission group,” Dr. Moriconi said.

He highlighted how none of the patients who had achieved remission had used insulin, whereas 12% of those who had relapsed and half (52%) of those who remained with type 2 diabetes had used insulin (P < .0001).

Patients who achieved remission at 1, 5, and 10 years were more likely to have had diabetes for less than 5 years than those who remained with type 2 diabetes. The average duration of diabetes was 2 years in those achieving remission versus 8 years in those who had relapsed and 13 years in those who had remained diabetic (P < .0001).

Logistic regression analysis, which adjusted for all major confounding factors such as age, sex, and type of surgery, showed that only the duration of diabetes and insulin therapy before surgery were the only predictors of long-term diabetes remission.

The study had no commercial funding. Dr. Moriconi and Dr. Vilsbøll had no conflicts of interest to disclose.

SOURCE: Moriconi D. EASD 2020, Oral presentation 120.

Type 2 diabetes patients who had never used insulin showed sustained remission 10 years after bariatric surgery in a prospective study of 85 patients.

Having diabetes for less than 5 years was also predictive of achieving long-term diabetes remission, Diego Moriconi, MD, of the University of Pisa (Italy) and presenting study investigator, reported at the virtual annual meeting of the European Association for the Study of Diabetes.

“Weight loss was associated with type 2 diabetes remission 1 year after surgery, but it had no impact on the long-term relapse of diabetes,” Dr. Moriconi said.

The findings are important, commented Tina Vilsbøll, MD, DMSc, chief consultant at the Steno Diabetes Centre Copenhagen, who chaired the session. They’re important because they would help “to set the expectations for patients before they have surgery, what to expect in respect to resolution or remission of diabetes.”

If patients were taking insulin, for instance, the take home would seem to be not to expect too much in terms of remission of their diabetes, Dr. Vilsbøll said. She added: “Usually I am not a big fan of [relying on] diabetes duration, because often we know that patients with type 2 diabetes have had diabetes for a long time before they’re actually diagnosed.” However, “it seems to be very important here.”

Dr. Moriconi reported the findings of an observational study that had started in 2006 and recruited individuals about to undergo bariatric surgery for type 2 diabetes. Participants were evaluated before surgery and every 6-12 months after, undergoing various clinical and laboratory investigations, for a period of 10 years.

The majority of the recruited patients (76%) were women. Most (also 76%) had undergone gastric bypass (Roux-en-Y) surgery, and the remainder had undergone sleeve gastrectomy. Both types of surgery were equally as good at getting people into remission, as defined by the American Diabetes Association Standards of Medical Care in Diabetes, Dr. Moriconi said. As such, remission was achieved if the fasting blood glucose fell below 100 mg/dL and the hemoglobin A1c below 5.7%.

In the first year following surgery, 75% of patients had met diabetes remission criteria. This fell to 61% of patients after 5 years, and to 55% at 10 years. At each of these time points, 25% of patients had type 2 diabetes, with 14% relapsing back at 5 years and 20% at 10 years.

Dr. Moriconi pointed out some of the different characteristics of the 47 patients who had achieved diabetes remission at 10 years, compared with the 17 who had “relapsed” back to having type 2 diabetes and the 21 who had remained with type 2 diabetes.

The decrease in body mass index achieved at 10 years was no different between the three groups. However, 1 year after surgery, there had been a significantly greater drop in body in those who achieved remission, compared with those who did not (P = .04).

“Glycemic control improved with time in all the three groups after bariatric surgery, although more markedly so in the remission group,” Dr. Moriconi said.

He highlighted how none of the patients who had achieved remission had used insulin, whereas 12% of those who had relapsed and half (52%) of those who remained with type 2 diabetes had used insulin (P < .0001).

Patients who achieved remission at 1, 5, and 10 years were more likely to have had diabetes for less than 5 years than those who remained with type 2 diabetes. The average duration of diabetes was 2 years in those achieving remission versus 8 years in those who had relapsed and 13 years in those who had remained diabetic (P < .0001).

Logistic regression analysis, which adjusted for all major confounding factors such as age, sex, and type of surgery, showed that only the duration of diabetes and insulin therapy before surgery were the only predictors of long-term diabetes remission.

The study had no commercial funding. Dr. Moriconi and Dr. Vilsbøll had no conflicts of interest to disclose.

SOURCE: Moriconi D. EASD 2020, Oral presentation 120.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Not only the prevalence, but the impact of nonalcoholic fatty liver disease (NAFLD) is increasing in much of the world, Arun J. Sanyal, MD, said in a virtual presentation at the meeting jointly provided by Rutgers and Global Academy for Medical Education. “It is currently estimated that the number of people living with cirrhosis or with decompensated cirrhosis will increase two- to threefold from 2015 to 2030,” which underlines the public health impact and the need for improved treatment paradigms, he emphasized.

“The thing to remember about NAFLD is that it does not exist in a vacuum,” Dr. Sanyal said. NAFLD is a multisystem disorder. Most patients have concomitant cardiovascular disease, but others may have type 2 diabetes, hypertension, and dyslipidemia, all of which are now accepted as risk factors for nonalcoholic steatohepatitis (NASH), he said.

“What ties these conditions together is metabolic stress leading to systemic inflammation and fibrosis. This is primarily due to diet-induced obesity. If you think about treating all of these competing risks to the patient’s life, the optimal way is to treat the root cause,” he said.

Various options exist to manage the conditions that can lead to NASH, but several of these also appear promising as a treatment of NASH, Dr. Sanyal said. Glucagonlike peptide–1 agonists and sodium-glucose transporter 2 inhibitors have been shown to improve multiple outcomes of interest in type 2 diabetes. However, insulin can cause weight gain at the expense of controlling HbA1C levels, he said.

Bariatric surgery can improve histology, but many patients with advanced fibrosis do not demonstrate improvement in fibrosis. Also, bariatric surgery has its own associated morbidity, including an increased suicide rate across multiple studies, Dr. Sanyal noted.

A new and interesting option is duodenal mucosal resurfacing (DMR) “a novel, minimally invasive outpatient upper-endoscopic procedure,” said Dr. Sanyal. DMR involves use of a catheter to perform a submucosal lift and hydrothermal mucosal ablation, prompting healthy epithelial regrowth, he explained. “The mucosa sloughs off, fresh epithelium grows in, and the hormonal signal from the gut to the rest of the body is restored to a more normal pattern,” he noted.

In the REVITA-2 study of patients with diabetes and NAFLD, the average fat loss was 5.4% in those randomized to DMR vs. 2.4% in sham-procedure patients and represented “quite significant defatting of the liver,” Dr. Sanyal said.

Dr. Sanyal then focused on fatty liver disease. “The first step when you see a patient with fatty liver disease is to see how scarred is the liver, and whether the patient has silent cirrhosis. The more scarred the liver, the greater risk of liver-related outcomes,” he said. The goal of therapy for these patients is to reduce the risk of progression to cirrhosis, he added. Dr. Sanyal recommended evaluating fibrosis using the Fibrosis 4 score (Fib4). “If the Fib4 is less than 1.3, the likelihood of significant scarring in the liver is less than 10%,” he said. On the other hand, a Fib4 greater than 2.67 suggests advanced fibrosis, he noted.

Overall, the goals of treatment for NASH patients are to prevent cirrhosis, reduce decompensation, and prevent hepatocellular carcinoma, said Dr. Sanyal.

“The ideal drug for NASH should also help other end organs, or at least be neutral,” said Dr. Sanyal.

Current frontline therapies for precirrhotic NASH include thiazolidinediones (TZD), farnesoid X receptor (FXR)/fibroblast growth factor 19 (FGF-19), FGF21, thyroxine B-R, and glucagonlike peptide-1. Clinical evidence varies based on different populations, endpoints, assessment methods, and treatment duration, he said.

Looking ahead to the next decade, a NASH management paradigm will likely play out that can be applied in the clinic today, Dr. Sanyal said. First, make an initial assessment of the status of the end organs. Start with a weight-loss regimen; use statins and GLP-1 and SGLT2 inhibitors as needed. Follow and reassess, and if the patient still has disease, progress to targeted therapy for active NASH while continuing to encourage weight loss and healthy living, he said.

“The ultimate proof that what we are doing is working is that we are improving mortality, reducing health care costs, and improving patients’ function and quality of life,” he concluded.

Dr. Sanyal is president of Sanyal Biotechnologies. He also disclosed stock options for Durect, Exhalenz, Galmed, Genfit, Immuton, Indalo, and Tiziana, as well as various relationships with Allergan, AMRA, Astra Zeneca-Medimmune, Birdrock, Boehringer Ingelheim, Bristol Myers, Echosense, GE, Genentech, Gilead, Hemoshear, IFMO, Innovate, Intercept, Lilly, Lipocine, Merck, Novartis, Novo Nordisk, OWL, Pfizer, RedX, Sundise, Tern, and Zydus.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

As may be expected, lifestyle risk factors, including physical activity and diet, are found to be more influential in determining type 2 diabetes risk within a married couple than physiologic factors such as glucose tolerance or insulin sensitivity, researchers have shown.

“Essentially, these data suggest that couple-based interventions targeting spouses’ similarities might be [an] efficient way of delivering lifestyle interventions,” said study lead Omar Silverman-Retana, MD, PhD.

“We identified that spousal concordance was strongest for behavioral risk factors, in particular physical activity and diet,” he told Medscape Medical News in an interview.

Silverman-Retana, of Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, reported the findings in a poster at this year’s annual meeting of the European Association for the Study of Diabetes (EASD), held online because of the coronavirus pandemic.

Effectively, concordance was found to be weaker in the pathophysiologic markers because these are more biologically determined compared with lifestyle factors.

Janice Kiecolt-Glaser, PhD, is a marital biobehavioral researcher who is interested in spousal concordance for many chronic health conditions.

This “research is part of a growing body of evidence that carries a clear message: Be careful whom you marry, your life may depend on it!” she explained.

“Your partner’s behavior definitely influences your own, and in the case of diabetes, the researchers have found clear behavioral links, and those make sense,” she told Medscape Medical News.

“In addition, data from our lab and others show that the gut microbiomes of cohabiting couples are more similar than those of unrelated pairs,” noted Kiecolt-Glaser, who is professor of psychiatry and behavioral Health at Ohio State University College of Medicine in Columbus.

“Diet and exercise both have substantial influences on the gut microbiome, and there is growing evidence that the gut microbiome contributes to risk for diabetes. This research fits with, and extends, what we know.”
 

A comprehensive picture of mechanisms leading to diabetes

The research led by Silverman-Retana and colleagues comprised a cross-sectional analysis of couples who participated in The Maastricht Study, an extensive phenotyping trial that focuses on the causes of type 2 diabetes, its classic complications, and its emerging comorbidities.

The researchers measured a comprehensive list of lifestyle and physiologic indicators, and using the social network aspect of the study, identified 172 couples with complete information for the final analysis.

Spousal concordance in lifestyle factors and pathophysiologic mechanisms of type 2 diabetes, including beta cell function and insulin sensitivity, were determined using regression analysis. Risk factors included waist circumference, percentage body fat, physical activity, sedentary time, the Dutch Healthy Diet Index (DHDI), and total energy consumption.

In addition, the researchers assessed glucose metabolism status using fasting and 2-hour plasma glucose, as well as HbA1c, and they also derived beta cell function indices using a seven-time point glucose tolerance test, and insulin sensitivity.

“Most importantly, we measured risk factors and pathophysiologic factors in the same study, and to the same level of detail in both partners, providing a more comprehensive picture of the mechanisms that lead to type 2 diabetes,” Silverman-Retana highlighted.

There have been previous studies addressing disease risk and couples’ concordance. A prior study, also by Silverman-Retana and colleagues at Aarhus University, found a link between the weight of one spouse and the chances of a diagnosis of type 2 diabetes in the other spouse.

Another study, reported by Medscape Medical News  in 2018, showed that when one spouse tried to lose weight with a weight management program, the other ‘untreated’ spouse was also likely to drop some weight.

Silverman-Retana noted that other research examining the similarities and differences within couples has investigated physical activity using self-reported questionnaires, but the current study used accelerometer data.  “These provide a more precise measure of physical activity,” he said, in pointing out one way in which the new study differs from previous ones. 

The findings suggest that for men, the strongest spousal concordance was for the Dutch Healthy Diet Index (DHDI), meaning that a one unit increase in wives’ DHDI was associated with a 0.53 unit difference in the men’s DHDI.

For women, the strongest concordance was for the time spent in high intensity physical activity, such that a one unit increase in husbands’ time spent in high intensity physical activity was associated with a 0.36 unit difference in women’s time spent in high intensity physical activity.

“If we compare the concordance, it weakens as we move downstream to the immediate causal risk factors of type 2 diabetes,” explained Silverman-Retana. “The weakest concordance was found in beta cell function indices and glucose metabolism indicators because these are more biologically determined.”

Concordance is mainly explained by the fact that we tend to choose a partner who has similar characteristics to our own, in terms of social class and/or educational level, smoking status, exercise habits and diet, explained the researcher.

“It would be interesting to know how behavioral similarity depends on the length of marriage or time as a couple. Future studies will need to look into this,” he concluded.   

Silverman-Retana and Kiecolt-Glaser have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.

Persons with type 2 diabetes may be at heightened risk for developing vascular dementia than other types of dementia, a team of international researchers has found.

Compared with a nondiabetic control population, those with type 2 diabetes had a statistically significant 35% increased chance of having vascular dementia in a large observational study.

By comparison, the risk for nonvascular dementia was increased by a “more modest” 8%, said the researchers from the University of Glasgow and the University of Gothenburg (Sweden), while the risk for Alzheimer’s dementia appeared to be reduced by 8%.

The link between type 2 diabetes and dementia is not new, observed Carlos Celis-Morales, PhD, who presented the study’s findings at the virtual annual meeting of the European Association for the Study of Diabetes. With people living longer thanks to improved preventative strategies and treatments, there is a risk for developing other chronic conditions, such as dementia.

“A third of all dementia cases may be attributable to modifiable risk factors, among them type 2 diabetes, which accounts for 3.2% of all dementia cases,” said Dr. Celis-Morales, a research fellow at the University of Glasgow’s Institute of Cardiovascular and Medical Sciences.

“Although we know that diabetes is linked to dementia, what we don’t know really well is how much of this association between diabetes and dementia outcomes are explained by modifiable and nonmodifiable risk factors,” Dr. Celis-Morales added.

“Diabetes and dementia share certain risk factors,” commented coinvestigator Naveed Sattar, MD, in a press release issued by the EASD. These include obesity, smoking, and lack of physical activity and might explain part of the association between the two conditions.

Dr. Sattar said that the heightened vascular dementia risk found in the study was “in itself an argument for preventive measures such as healthier lifestyle,” adding that “the importance of prevention is underscored by the fact that, for the majority of dementia diseases, there is no good treatment.”

Using data from the Swedish National Diabetes Register, the research team set out to determine the extent to which type 2 diabetes was associated with dementia and the incidence of different subtypes of dementia. They also looked to see if there were any associations with blood glucose control and what risk factors may be involved.

In total, data on 378,299 individuals with type 2 diabetes were compared with data on 1,886,022 similarly aged (average, 64 years) and gender-matched controls from the general population.

After a mean 7 years of follow-up, 10,143 people with and 46,479 people without type 2 diabetes developed dementia. Nonvascular dementia was the most common type of dementia recorded, followed by Alzheimer’s disease and then vascular dementia.

“Within type 2 diabetes individuals, poor glycemic [control] increased the risk of dementia especially for vascular dementia and nonvascular dementia. However, these associations were not as evident for Alzheimer’s disease,” Dr. Celis-Morales reported.

Comparing those with hemoglobin bA1c of less than 52 mmol/mol (7%) with those whose A1c was above 87 mmol/mol (10.1%), there was 93% increase in the risk for vascular dementia, a 67% increase in the risk for nonvascular dementia, and a 34% higher risk for Alzheimer’s disease–associated dementia.

“We have focused on high levels of HbA1c, but what happens if you have really low limits? It’s something we’re working on right now,” Dr. Celis-Morales said.

Importantly, cardiovascular-related risk factors – some of which, like systolic blood pressure and body weight, were potentially modifiable – accounted for more than 40% of the risk for dementia in type 2 diabetes. This suggests that a large percentage of the dementia risk could perhaps be addressed by identifying high-risk individuals and tailoring interventions accordingly.

“These are observational findings, so we need to be careful before we translate to any sort of recommendation,” Dr. Celis-Morales said.

The study was financed by the Swedish state under the agreement between the government and the county councils, the ALF agreement, as well as grant from the Novo Nordisk Foundation and the Swedish Association of Local Authorities and Regions. Dr. Celis-Morales and Dr. Sattar had no conflicts of interest.
 

SOURCE: Celis-Morales C et al. EASD 2020, Oral presentation 06.

Survival of U.S. patients who received a kidney transplant improved during 2000-2018, but the extent of improvement among patients whose end-stage kidney disease linked with diabetes lagged behind patients with renal disease unrelated to diabetes, based on a review of more than 250,000 U.S. renal transplant recipients from that period.

Mohammed Haneefa Nizamudeen/Getty Images

After adjustment for several demographic and clinical baseline differences, as well as for several characteristics of the organ donor, the analysis showed that patients with type 2 diabetes (T2D) had a significant 64% higher mortality rate following kidney transplant compared with patients without diabetes, while patients with type 1 diabetes (T1D) had a significant 94% increased relative rate of death, Jessica Harding, PhD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

The analyses that Dr. Harding reported also showed that, throughout the period examined, mortality rates following kidney transplant remained several times greater than the death rate of similar Americans who did not undergo renal replacement. By 2017, the standardized mortality ratio for patients with T2D following a kidney transplant was roughly fourfold greater than in similarly aged Americans in the general population who did undergo a transplant, while for patients with T1D the standardized mortality ratio compared with the general population was about sevenfold higher.

“Important disparities” for survival following kidney transplantation based on a specific diabetes etiology exist among U.S. patients, and further research should examine ways to better reduce posttransplant mortality in patients with diabetes, especially those with T1D, concluded Dr. Harding, an epidemiologist in the division of transplantation, department of surgery, at Emory University, Atlanta.

Issues surrounding kidney transplantation and postsurgical survival among patients with diabetes are important because these patients remain very susceptible to developing end-stage kidney disease and need for renal replacement. Adequate management of hyperglycemia, hypertension, and the adverse cardiovascular effects of immunosuppressive drugs might provide effective strategies for further mortality reductions among patients with diabetes following kidney transplant, she suggested.

The study used data collected in the United States Renal Data System during January 2000–August 2018, and included 258,188 adults who underwent a first-time, single kidney transplant at a U.S. center. About 20,000 patients had T1D (8%), about 59,000 (23%) had T2D, and the remaining 69% had no diabetes diagnosis. The data allowed for survival monitoring during a median follow-up of just over 6 years, during which more than 72,000 of the tracked patients (28%) died. The Renal Data System entries for 2017 also showed that 47% of U.S. patients with new end-stage renal disease had a diabetes etiology, Dr. Harding said.

The study received no commercial funding. Dr. Harding had no disclosures.

[email protected]

SOURCE: Harding J. EASD 2020. Oral presentation 66.

Survival of U.S. patients who received a kidney transplant improved during 2000-2018, but the extent of improvement among patients whose end-stage kidney disease linked with diabetes lagged behind patients with renal disease unrelated to diabetes, based on a review of more than 250,000 U.S. renal transplant recipients from that period.

Mohammed Haneefa Nizamudeen/Getty Images

After adjustment for several demographic and clinical baseline differences, as well as for several characteristics of the organ donor, the analysis showed that patients with type 2 diabetes (T2D) had a significant 64% higher mortality rate following kidney transplant compared with patients without diabetes, while patients with type 1 diabetes (T1D) had a significant 94% increased relative rate of death, Jessica Harding, PhD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

The analyses that Dr. Harding reported also showed that, throughout the period examined, mortality rates following kidney transplant remained several times greater than the death rate of similar Americans who did not undergo renal replacement. By 2017, the standardized mortality ratio for patients with T2D following a kidney transplant was roughly fourfold greater than in similarly aged Americans in the general population who did undergo a transplant, while for patients with T1D the standardized mortality ratio compared with the general population was about sevenfold higher.

“Important disparities” for survival following kidney transplantation based on a specific diabetes etiology exist among U.S. patients, and further research should examine ways to better reduce posttransplant mortality in patients with diabetes, especially those with T1D, concluded Dr. Harding, an epidemiologist in the division of transplantation, department of surgery, at Emory University, Atlanta.

Issues surrounding kidney transplantation and postsurgical survival among patients with diabetes are important because these patients remain very susceptible to developing end-stage kidney disease and need for renal replacement. Adequate management of hyperglycemia, hypertension, and the adverse cardiovascular effects of immunosuppressive drugs might provide effective strategies for further mortality reductions among patients with diabetes following kidney transplant, she suggested.

The study used data collected in the United States Renal Data System during January 2000–August 2018, and included 258,188 adults who underwent a first-time, single kidney transplant at a U.S. center. About 20,000 patients had T1D (8%), about 59,000 (23%) had T2D, and the remaining 69% had no diabetes diagnosis. The data allowed for survival monitoring during a median follow-up of just over 6 years, during which more than 72,000 of the tracked patients (28%) died. The Renal Data System entries for 2017 also showed that 47% of U.S. patients with new end-stage renal disease had a diabetes etiology, Dr. Harding said.

The study received no commercial funding. Dr. Harding had no disclosures.

[email protected]

SOURCE: Harding J. EASD 2020. Oral presentation 66.

Survival of U.S. patients who received a kidney transplant improved during 2000-2018, but the extent of improvement among patients whose end-stage kidney disease linked with diabetes lagged behind patients with renal disease unrelated to diabetes, based on a review of more than 250,000 U.S. renal transplant recipients from that period.

Mohammed Haneefa Nizamudeen/Getty Images

After adjustment for several demographic and clinical baseline differences, as well as for several characteristics of the organ donor, the analysis showed that patients with type 2 diabetes (T2D) had a significant 64% higher mortality rate following kidney transplant compared with patients without diabetes, while patients with type 1 diabetes (T1D) had a significant 94% increased relative rate of death, Jessica Harding, PhD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

The analyses that Dr. Harding reported also showed that, throughout the period examined, mortality rates following kidney transplant remained several times greater than the death rate of similar Americans who did not undergo renal replacement. By 2017, the standardized mortality ratio for patients with T2D following a kidney transplant was roughly fourfold greater than in similarly aged Americans in the general population who did undergo a transplant, while for patients with T1D the standardized mortality ratio compared with the general population was about sevenfold higher.

“Important disparities” for survival following kidney transplantation based on a specific diabetes etiology exist among U.S. patients, and further research should examine ways to better reduce posttransplant mortality in patients with diabetes, especially those with T1D, concluded Dr. Harding, an epidemiologist in the division of transplantation, department of surgery, at Emory University, Atlanta.

Issues surrounding kidney transplantation and postsurgical survival among patients with diabetes are important because these patients remain very susceptible to developing end-stage kidney disease and need for renal replacement. Adequate management of hyperglycemia, hypertension, and the adverse cardiovascular effects of immunosuppressive drugs might provide effective strategies for further mortality reductions among patients with diabetes following kidney transplant, she suggested.

The study used data collected in the United States Renal Data System during January 2000–August 2018, and included 258,188 adults who underwent a first-time, single kidney transplant at a U.S. center. About 20,000 patients had T1D (8%), about 59,000 (23%) had T2D, and the remaining 69% had no diabetes diagnosis. The data allowed for survival monitoring during a median follow-up of just over 6 years, during which more than 72,000 of the tracked patients (28%) died. The Renal Data System entries for 2017 also showed that 47% of U.S. patients with new end-stage renal disease had a diabetes etiology, Dr. Harding said.

The study received no commercial funding. Dr. Harding had no disclosures.

[email protected]

SOURCE: Harding J. EASD 2020. Oral presentation 66.

The more patients with type 2 diabetes exercise, the greater their drop in A1c, according to a new post hoc analysis of data collected during 6 months of supervised exercise.

This “dose-response” relationship between exercise and reductions in A1c held firm for those who did aerobic training or a mixture of aerobic and resistance exercises (combined), but not for those who did only resistance exercises, say Ronald J. Sigal, MD, and colleagues in their article published in the September issue of Medicine & Science in Sports & Exercise.

The findings “suggest that an increased volume of aerobic or combined aerobic and resistance exercise is associated with greater improvement in glycemic control,” say Dr. Sigal, a professor in the division of endocrinology and metabolism at the University of Calgary (Alta.) and colleagues.

In addition, the results “support aerobic and combined exercise prescriptions outlined in clinical practice guidelines … such as those published by the American Diabetes Association (Diabetes Care. 2016;39:2065-79),” they note.

Dr. Sigal was also a coauthor of the ADA position statement on exercise, physical activity, and diabetes.
 

Those who exercised the most saw biggest drop in A1c

In the new report, Dr. Sigal and coauthors note they are “unaware of previous studies exploring the relationship between adherence to prescribed exercise and change in glycemic control in patients with type 2 diabetes.”

The analysis used data collected from the DARE (Diabetes Aerobic and Resistance Exercise) trial, which randomized 251 patients with type 2 diabetes to a 6-month supervised exercise program or their usual habits (the latter were used as sedentary controls). The original DARE results showed that each of the three tested modes of supervised exercise – exclusively aerobic, exclusively resistance training, or a combination of both – resulted in a significant drop in average A1c level, compared with controls (Ann Int Med. 2007;147:357-69).  

This original study did not subdivide patients in the intervention groups by level of adherence to their exercise prescription.

The new analysis focused on the 185 patients randomized to one of the three exercise arms and tracked adherence by both self-recorded logs from patients and reports from the trainers who ran the exercise sessions.

The patients were an average of 54 years old, and slightly more than a third were women. Median A1c at baseline was about 7.7%. Median overall adherence to their exercise regimen was about 86% and was roughly similar in the three exercise subgroups.

The exercise prescription consisted of a 60-minute session (including warm-up and cool-down) three times weekly.

Those who did the most exercise saw the biggest improvements in A1c: a 20% increase in adherence (which correlated with an additional two sessions per month) was associated with a 0.15% decrease in A1c (P = .021)

When analyzed by type of exercise, both the subgroup that performed aerobic exercise only and the subgroup that did both aerobic and resistance exercise showed significant correlations with reductions in A1c. There was no significant association with A1c for the patients who did only resistance training.

Further subgroup analyses showed that significant relationships between exercise adherence and reduced glycemia were seen in only patients younger than 55 years old, men, and those with a baseline A1c ≥ 7.5%.

The researchers caution that the low number of patients in their analysis limits the statistical power and thereby interpretation of the findings, as does the post-hoc nature of the analysis.

DARE received no commercial funding. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The more patients with type 2 diabetes exercise, the greater their drop in A1c, according to a new post hoc analysis of data collected during 6 months of supervised exercise.

This “dose-response” relationship between exercise and reductions in A1c held firm for those who did aerobic training or a mixture of aerobic and resistance exercises (combined), but not for those who did only resistance exercises, say Ronald J. Sigal, MD, and colleagues in their article published in the September issue of Medicine & Science in Sports & Exercise.

The findings “suggest that an increased volume of aerobic or combined aerobic and resistance exercise is associated with greater improvement in glycemic control,” say Dr. Sigal, a professor in the division of endocrinology and metabolism at the University of Calgary (Alta.) and colleagues.

In addition, the results “support aerobic and combined exercise prescriptions outlined in clinical practice guidelines … such as those published by the American Diabetes Association (Diabetes Care. 2016;39:2065-79),” they note.

Dr. Sigal was also a coauthor of the ADA position statement on exercise, physical activity, and diabetes.
 

Those who exercised the most saw biggest drop in A1c

In the new report, Dr. Sigal and coauthors note they are “unaware of previous studies exploring the relationship between adherence to prescribed exercise and change in glycemic control in patients with type 2 diabetes.”

The analysis used data collected from the DARE (Diabetes Aerobic and Resistance Exercise) trial, which randomized 251 patients with type 2 diabetes to a 6-month supervised exercise program or their usual habits (the latter were used as sedentary controls). The original DARE results showed that each of the three tested modes of supervised exercise – exclusively aerobic, exclusively resistance training, or a combination of both – resulted in a significant drop in average A1c level, compared with controls (Ann Int Med. 2007;147:357-69).  

This original study did not subdivide patients in the intervention groups by level of adherence to their exercise prescription.

The new analysis focused on the 185 patients randomized to one of the three exercise arms and tracked adherence by both self-recorded logs from patients and reports from the trainers who ran the exercise sessions.

The patients were an average of 54 years old, and slightly more than a third were women. Median A1c at baseline was about 7.7%. Median overall adherence to their exercise regimen was about 86% and was roughly similar in the three exercise subgroups.

The exercise prescription consisted of a 60-minute session (including warm-up and cool-down) three times weekly.

Those who did the most exercise saw the biggest improvements in A1c: a 20% increase in adherence (which correlated with an additional two sessions per month) was associated with a 0.15% decrease in A1c (P = .021)

When analyzed by type of exercise, both the subgroup that performed aerobic exercise only and the subgroup that did both aerobic and resistance exercise showed significant correlations with reductions in A1c. There was no significant association with A1c for the patients who did only resistance training.

Further subgroup analyses showed that significant relationships between exercise adherence and reduced glycemia were seen in only patients younger than 55 years old, men, and those with a baseline A1c ≥ 7.5%.

The researchers caution that the low number of patients in their analysis limits the statistical power and thereby interpretation of the findings, as does the post-hoc nature of the analysis.

DARE received no commercial funding. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The more patients with type 2 diabetes exercise, the greater their drop in A1c, according to a new post hoc analysis of data collected during 6 months of supervised exercise.

This “dose-response” relationship between exercise and reductions in A1c held firm for those who did aerobic training or a mixture of aerobic and resistance exercises (combined), but not for those who did only resistance exercises, say Ronald J. Sigal, MD, and colleagues in their article published in the September issue of Medicine & Science in Sports & Exercise.

The findings “suggest that an increased volume of aerobic or combined aerobic and resistance exercise is associated with greater improvement in glycemic control,” say Dr. Sigal, a professor in the division of endocrinology and metabolism at the University of Calgary (Alta.) and colleagues.

In addition, the results “support aerobic and combined exercise prescriptions outlined in clinical practice guidelines … such as those published by the American Diabetes Association (Diabetes Care. 2016;39:2065-79),” they note.

Dr. Sigal was also a coauthor of the ADA position statement on exercise, physical activity, and diabetes.
 

Those who exercised the most saw biggest drop in A1c

In the new report, Dr. Sigal and coauthors note they are “unaware of previous studies exploring the relationship between adherence to prescribed exercise and change in glycemic control in patients with type 2 diabetes.”

The analysis used data collected from the DARE (Diabetes Aerobic and Resistance Exercise) trial, which randomized 251 patients with type 2 diabetes to a 6-month supervised exercise program or their usual habits (the latter were used as sedentary controls). The original DARE results showed that each of the three tested modes of supervised exercise – exclusively aerobic, exclusively resistance training, or a combination of both – resulted in a significant drop in average A1c level, compared with controls (Ann Int Med. 2007;147:357-69).  

This original study did not subdivide patients in the intervention groups by level of adherence to their exercise prescription.

The new analysis focused on the 185 patients randomized to one of the three exercise arms and tracked adherence by both self-recorded logs from patients and reports from the trainers who ran the exercise sessions.

The patients were an average of 54 years old, and slightly more than a third were women. Median A1c at baseline was about 7.7%. Median overall adherence to their exercise regimen was about 86% and was roughly similar in the three exercise subgroups.

The exercise prescription consisted of a 60-minute session (including warm-up and cool-down) three times weekly.

Those who did the most exercise saw the biggest improvements in A1c: a 20% increase in adherence (which correlated with an additional two sessions per month) was associated with a 0.15% decrease in A1c (P = .021)

When analyzed by type of exercise, both the subgroup that performed aerobic exercise only and the subgroup that did both aerobic and resistance exercise showed significant correlations with reductions in A1c. There was no significant association with A1c for the patients who did only resistance training.

Further subgroup analyses showed that significant relationships between exercise adherence and reduced glycemia were seen in only patients younger than 55 years old, men, and those with a baseline A1c ≥ 7.5%.

The researchers caution that the low number of patients in their analysis limits the statistical power and thereby interpretation of the findings, as does the post-hoc nature of the analysis.

DARE received no commercial funding. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.