Diabetes

When scientists discovered the band of hemoglobin A_1c during electrophoresis in the 1950s and 1960s and discerned it was elevated in patients with diabetes, little did they know the important role it would play in the diagnosis and treatment of diabetes in the decades to come.^1–3 Despite some caveats, a hemoglobin A_1c level of 6.5% or higher is diagnostic of diabetes across most populations, and hemoglobin A_1c goals ranging from 6.5% to 7.5% have been set for different subsets of patients depending on comorbidities, complications, risk of hypoglycemia, life expectancy, disease duration, patient preferences, and available resources.⁴

With a growing number of medications for diabetes—insulin in its various formulations and 11 other classes—hemoglobin A_1c targets can now be tailored to fit individual patient profiles. Although helping patients attain their glycemic goals is paramount, other factors should be considered when prescribing or changing a drug treatment regimen, such as cardiovascular risk reduction, weight control, avoidance of hypoglycemia, and minimizing out-of-pocket drug costs (Table 1).

CARDIOVASCULAR BENEFIT

Patients with type 2 diabetes have a 2 to 3 times higher risk of clinical atherosclerotic disease, according to 20 years of surveillance data from the Framingham cohort.⁵

Mixed results with intensive treatment

Reducing cardiovascular risk remains an important goal in diabetes management, but unfortunately, data from the long-term clinical trials aimed at reducing macrovascular risk with intensive glycemic management have been conflicting.

The United Kingdom Prospective Diabetes Study (UKPDS),⁶ which enrolled more than 4,000 patients with newly diagnosed type 2 diabetes, did not initially show a statistically significant difference in the incidence of myocardial infarction with intensive control vs conventional control, although intensive treatment did reduce the incidence of microvascular disease. However, 10 years after the trial ended, the incidence was 15% lower in the intensive-treatment group than in the conventional-treatment group, and the difference was statistically significant.⁷

A 10-year follow-up analysis of the Veterans Affairs Diabetes Trial (VADT)⁸ showed that patients who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1,000 person-years than those assigned to standard therapy, but no improvement in median overall survival. The hemoglobin A_1c levels achieved during the trial were 6.9% and 8.4%, respectively.

In 2008, the US Food and Drug Administration (FDA)⁹ mandated that all new applications for diabetes drugs must include cardiovascular outcome studies. Therefore, we now have data on the cardiovascular benefits of two antihyperglycemic drug classes—incretins and sodium-glucose cotransporter 2 (SGLT2) inhibitors, making them attractive medications to target both cardiac and glucose concerns.

Incretins

The incretin drugs comprise 2 classes, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors.

Liraglutide. The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial¹⁰ compared liraglutide (a GLP-1 receptor agonist) and placebo in 9,000 patients with diabetes who either had or were at high risk of cardiovascular disease. Patients in the liraglutide group had a lower risk of the primary composite end point of death from cardiovascular causes or the first episode of nonfatal (including silent) myocardial infarction or nonfatal stroke, and a lower risk of cardiovascular death, all-cause mortality, and microvascular events than those in the placebo group. The number of patients who would need to be treated to prevent 1 event in 3 years was 66 in the analysis of the primary outcome and 98 in the analysis of death from any cause.⁹

Lixisenatide. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial¹¹ studied the effect of the once-daily GLP-1 receptor agonist lixisenatide on cardiovascular outcomes in 6,000 patients with type 2 diabetes with a recent coronary event. In contrast to LEADER, ELIXA did not show a cardiovascular benefit over placebo.

Exenatide. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL)¹² assessed another GLP-1 extended-release drug, exenatide, in 14,000 patients, 73% of whom had established cardiovascular disease. In those patients, the drug had a modest benefit in terms of first occurrence of any component of the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (3-component major adverse cardiac event [MACE] outcome) in a time-to-event analysis, but the results were not statistically significant. However, the drug did significantly reduce all-cause mortality.

Semaglutide, another GLP-1 receptor agonist recently approved by the FDA, also showed benefit in patients who had cardiovascular disease or were at high risk, with significant reduction in the primary composite end point of death from cardiovascular causes or the first occurrence of nonfatal myocardial infarction (including silent) or nonfatal stroke.¹³

Dulaglutide, a newer GLP-1 drug, was associated with significantly reduced major adverse cardiovascular events (a composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in about 9,900 patients with diabetes, with a median follow-up of more than 5 years. Only 31% of the patients in the trial had established cardiovascular disease.¹⁴

Comment. GLP-1 drugs as a class are a good option for patients with diabetes who require weight loss, and liraglutide is now FDA-approved for reduction of cardiovascular events in patients with type 2 diabetes with established cardiovascular disease. However, other factors should be considered when prescribing these drugs: they have adverse gastrointestinal effects, the cardiovascular benefit was not a class effect, they are relatively expensive, and they must be injected. Also, they should not be prescribed concurrently with a DPP-4 inhibitor because they target the same pathway.

The other class of diabetes drugs that have shown cardiovascular benefit are the SGLT2 inhibitors.

Empagliflozin. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG)¹⁵ compared the efficacy of empagliflozin vs placebo in 7,000 patients with diabetes and cardiovascular disease and showed relative risk reductions of 38% in death from cardiovascular death, 31% in sudden death, and 35% in heart failure hospitalizations. Empagliflozin also showed benefit in terms of progression of kidney disease and occurrence of clinically relevant renal events in this population.¹⁶

Canagliflozin also has cardiovascular outcome data and showed significant benefit when compared with placebo in the primary outcome of the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, but no significant effects on cardiovascular death or all-cause mortality.¹⁷ Data from this trial also suggested a nonsignificant benefit of canagliflozin in decreasing progression of albuminuria and in the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate (eGFR), the need for renal replacement therapy, or death from renal causes.

The above data led to an additional indication from the FDA for empagliflozin—and recently, canagliflozin—to prevent cardiovascular death in patients with diabetes with established disease, but other factors should be considered when prescribing them. Patients taking canagliflozin showed a significantly increased risk of amputation. SGLT2 inhibitors as a class also increase the risk of genital infections in men and women; this is an important consideration since patients with diabetes complain of vaginal fungal and urinary tract infections even without the use of these drugs. A higher incidence of fractures with canagliflozin should also be considered when using these medications in elderly and osteoporosis-prone patients at high risk of falling.

Dapagliflozin, the third drug in this class, was associated with a lower rate of hospitalization for heart failure in about 17,160 patients—including 10,186 without atherosclerotic cardiovascular disease—who were followed for a median of 4.2 years.¹⁸ It did not show benefit for the primary safety outcome, a composite of major adverse cardiovascular events defined as cardiovascular death, myocardial infarction, or ischemic stroke.

WEIGHT MANAGEMENT

Weight loss can help overweight patients reach their hemoglobin A_1c target.

Metformin should be continued as other drugs are added because it does not induce weight gain and may help with weight loss of up to 2 kg as shown in the Diabetes Prevention Program Outcomes Study.¹⁹

GLP-1 receptor agonists and SGLT2 inhibitors help with weight loss and are good additions to a basal insulin regimen to minimize weight gain.

Liraglutide was associated with a mean weight loss of 2.3 kg over 36 months of treatment compared with placebo in the LEADER trial.¹⁰

In the Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6),²⁰ the mean body weight in the semaglutide group, compared with the placebo group, was 2.9 kg lower in the group receiving a lower dose and 4.3 kg lower in the group receiving a higher dose of the drug.

In a 24-week trial in 182 patients with type 2 diabetes inadequately controlled on metformin, dapagliflozin produced a statistically significant weight reduction of 2.08 kg (95% confidence interval 2.84–1.31; P < .0001) compared with placebo.²¹

Lifestyle changes aimed at weight management should be emphasized and discussed at every visit.

HYPOGLYCEMIA RISK

Hypoglycemia is a major consideration when tailoring hemoglobin A_1c targets. In the Action to Control Cardiovascular Risk (ACCORD) trial,²² severe, symptomatic hypoglycemia increased the risk of death in both the intensive and conventional treatment groups. In VADT, the occurrence of a recent severe hypoglycemic event was the strongest independent predictor of death within 90 days. Further analysis showed that even though serious hypoglycemia occurred more often in the intensive therapy group, it was associated with progression of coronary artery calcification in the standard therapy group.²³ Hence, it is imperative that tight glycemic control not be achieved at the cost of severe or recurrent hypoglycemia.

In terms of hypoglycemia, metformin is an excellent medication. The American Diabetes Association²⁴ recommends metformin as the first-line therapy for newly diagnosed diabetes. Long-term follow-up data from UKPDS showed that metformin decreased mortality and the incidence of myocardial infarction and lowered treatment costs as well as the overall risk of hypoglycemia.²⁵ When prescribed, it should be titrated to the highest dose.

The FDA²⁶ has changed the prescribing information for metformin in patients with renal impairment. Metformin should not be started if the eGFR is less than 45 mL/min/1.73 m², but it can be continued if the patient is already receiving it and the eGFR is between 30 and 45. Previously, creatinine levels were used to define renal impairment and suitability for metformin. This change has increased the number of patients who can benefit from this medication.

In patients who have a contraindication to metformin, DPP-4 inhibitors can be considered, as they carry a low risk of hypoglycemia as well. Sulfonylureas should be used with caution in these patients, especially if their oral intake is variable. When sulfonylureas were compared to the DPP-4 inhibitor sitagliptin as an add-on to metformin, the rate of hypoglycemia was 32% in the sulfonylurea group vs 5% in the sitagliptin group.²⁷

Of the sulfonylureas, glipizide and glimepiride are better than glyburide because of a comparatively lower risk of hypoglycemia and a higher selectivity for binding the K_ATP channel on the pancreatic beta cell.²⁸

Meglitinides can be a good option for patients who skip meals, but they are more expensive than other generic oral hypoglycemic agents and require multiple daily dosing.

GLP-1 analogues also have a low risk of hypoglycemia but are only available in injectable formulations. Patients must be willing and able to perform the injections themselves.²⁹

In 2010, among US residents age 65 and older, 10.9 million (about 27%) had diabetes,³⁰ and this number is projected to increase to 26.7 million by 2050.³¹ This population is prone to hypoglycemia when treated with insulin and sulfonylureas. An injury sustained by a fall induced by hypoglycemia can be life-altering. In addition, no randomized clinical trials show the effect of tight glycemic control on complications in older patients with diabetes because patients older than 80 are often excluded.

A reasonable goal suggested by the European Diabetes Working Party for Older People 2011³² and reiterated by the American Geriatrics Society in 2013³³ is a hemoglobin A_1c between 7% and 7.5% for relatively healthy older patients and 7.5% to 8% or 8.5% in frail elderly patients with diabetes.

Consider prescribing medications that carry a low risk of hypoglycemia, can be dose-adjusted for kidney function, and do not rely on manual dexterity for administration (ie, do not require patients to give themselves injections). These include metformin and DPP-4 inhibitors.

DRUG COMBINATIONS

Polypharmacy is a concern for all patients with diabetes, especially since it increases the risk of drug interactions and adverse effects, increases out-of-pocket costs, and decreases the likelihood that patients will remain adherent to their treatment regimen. The use of combination medications can reduce the number of pills or injections required, as well as copayments.

Due to concern for multiple drug-drug interactions (and also due to the progressive nature of diabetes), many people with type 2 diabetes are given insulin in lieu of pills to lower their blood glucose. In addition to premixed insulin combinations (such as combinations of neutral protamine Hagedorn and regular insulin or combinations of insulin analogues), long-acting basal insulins can now be prescribed with a GLP-1 drug in fixed-dose combinations such as insulin glargine plus lixisenatide and insulin degludec plus liraglutide.

COST CONSIDERATIONS

It is important to discuss medication cost with patients, because many newer diabetic drugs are expensive and add to the financial burden of patients already paying for multiple medications, such as antihypertensives and statins.

Metformin and sulfonylureas are less expensive alternatives for patients who cannot afford GLP-1 analogues or SGLT2 inhibitors. Even within the same drug class, the formulary-preferred drug may be cheaper than the nonformulary alternative. Thus, it is helpful to research formulary alternatives before discussing treatment regimens with patients.

When scientists discovered the band of hemoglobin A_1c during electrophoresis in the 1950s and 1960s and discerned it was elevated in patients with diabetes, little did they know the important role it would play in the diagnosis and treatment of diabetes in the decades to come.^1–3 Despite some caveats, a hemoglobin A_1c level of 6.5% or higher is diagnostic of diabetes across most populations, and hemoglobin A_1c goals ranging from 6.5% to 7.5% have been set for different subsets of patients depending on comorbidities, complications, risk of hypoglycemia, life expectancy, disease duration, patient preferences, and available resources.⁴

With a growing number of medications for diabetes—insulin in its various formulations and 11 other classes—hemoglobin A_1c targets can now be tailored to fit individual patient profiles. Although helping patients attain their glycemic goals is paramount, other factors should be considered when prescribing or changing a drug treatment regimen, such as cardiovascular risk reduction, weight control, avoidance of hypoglycemia, and minimizing out-of-pocket drug costs (Table 1).

CARDIOVASCULAR BENEFIT

Patients with type 2 diabetes have a 2 to 3 times higher risk of clinical atherosclerotic disease, according to 20 years of surveillance data from the Framingham cohort.⁵

Mixed results with intensive treatment

Reducing cardiovascular risk remains an important goal in diabetes management, but unfortunately, data from the long-term clinical trials aimed at reducing macrovascular risk with intensive glycemic management have been conflicting.

The United Kingdom Prospective Diabetes Study (UKPDS),⁶ which enrolled more than 4,000 patients with newly diagnosed type 2 diabetes, did not initially show a statistically significant difference in the incidence of myocardial infarction with intensive control vs conventional control, although intensive treatment did reduce the incidence of microvascular disease. However, 10 years after the trial ended, the incidence was 15% lower in the intensive-treatment group than in the conventional-treatment group, and the difference was statistically significant.⁷

A 10-year follow-up analysis of the Veterans Affairs Diabetes Trial (VADT)⁸ showed that patients who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1,000 person-years than those assigned to standard therapy, but no improvement in median overall survival. The hemoglobin A_1c levels achieved during the trial were 6.9% and 8.4%, respectively.

In 2008, the US Food and Drug Administration (FDA)⁹ mandated that all new applications for diabetes drugs must include cardiovascular outcome studies. Therefore, we now have data on the cardiovascular benefits of two antihyperglycemic drug classes—incretins and sodium-glucose cotransporter 2 (SGLT2) inhibitors, making them attractive medications to target both cardiac and glucose concerns.

Incretins

The incretin drugs comprise 2 classes, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors.

Liraglutide. The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial¹⁰ compared liraglutide (a GLP-1 receptor agonist) and placebo in 9,000 patients with diabetes who either had or were at high risk of cardiovascular disease. Patients in the liraglutide group had a lower risk of the primary composite end point of death from cardiovascular causes or the first episode of nonfatal (including silent) myocardial infarction or nonfatal stroke, and a lower risk of cardiovascular death, all-cause mortality, and microvascular events than those in the placebo group. The number of patients who would need to be treated to prevent 1 event in 3 years was 66 in the analysis of the primary outcome and 98 in the analysis of death from any cause.⁹

Lixisenatide. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial¹¹ studied the effect of the once-daily GLP-1 receptor agonist lixisenatide on cardiovascular outcomes in 6,000 patients with type 2 diabetes with a recent coronary event. In contrast to LEADER, ELIXA did not show a cardiovascular benefit over placebo.

Exenatide. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL)¹² assessed another GLP-1 extended-release drug, exenatide, in 14,000 patients, 73% of whom had established cardiovascular disease. In those patients, the drug had a modest benefit in terms of first occurrence of any component of the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (3-component major adverse cardiac event [MACE] outcome) in a time-to-event analysis, but the results were not statistically significant. However, the drug did significantly reduce all-cause mortality.

Semaglutide, another GLP-1 receptor agonist recently approved by the FDA, also showed benefit in patients who had cardiovascular disease or were at high risk, with significant reduction in the primary composite end point of death from cardiovascular causes or the first occurrence of nonfatal myocardial infarction (including silent) or nonfatal stroke.¹³

Dulaglutide, a newer GLP-1 drug, was associated with significantly reduced major adverse cardiovascular events (a composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in about 9,900 patients with diabetes, with a median follow-up of more than 5 years. Only 31% of the patients in the trial had established cardiovascular disease.¹⁴

Comment. GLP-1 drugs as a class are a good option for patients with diabetes who require weight loss, and liraglutide is now FDA-approved for reduction of cardiovascular events in patients with type 2 diabetes with established cardiovascular disease. However, other factors should be considered when prescribing these drugs: they have adverse gastrointestinal effects, the cardiovascular benefit was not a class effect, they are relatively expensive, and they must be injected. Also, they should not be prescribed concurrently with a DPP-4 inhibitor because they target the same pathway.

The other class of diabetes drugs that have shown cardiovascular benefit are the SGLT2 inhibitors.

Empagliflozin. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG)¹⁵ compared the efficacy of empagliflozin vs placebo in 7,000 patients with diabetes and cardiovascular disease and showed relative risk reductions of 38% in death from cardiovascular death, 31% in sudden death, and 35% in heart failure hospitalizations. Empagliflozin also showed benefit in terms of progression of kidney disease and occurrence of clinically relevant renal events in this population.¹⁶

Canagliflozin also has cardiovascular outcome data and showed significant benefit when compared with placebo in the primary outcome of the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, but no significant effects on cardiovascular death or all-cause mortality.¹⁷ Data from this trial also suggested a nonsignificant benefit of canagliflozin in decreasing progression of albuminuria and in the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate (eGFR), the need for renal replacement therapy, or death from renal causes.

The above data led to an additional indication from the FDA for empagliflozin—and recently, canagliflozin—to prevent cardiovascular death in patients with diabetes with established disease, but other factors should be considered when prescribing them. Patients taking canagliflozin showed a significantly increased risk of amputation. SGLT2 inhibitors as a class also increase the risk of genital infections in men and women; this is an important consideration since patients with diabetes complain of vaginal fungal and urinary tract infections even without the use of these drugs. A higher incidence of fractures with canagliflozin should also be considered when using these medications in elderly and osteoporosis-prone patients at high risk of falling.

Dapagliflozin, the third drug in this class, was associated with a lower rate of hospitalization for heart failure in about 17,160 patients—including 10,186 without atherosclerotic cardiovascular disease—who were followed for a median of 4.2 years.¹⁸ It did not show benefit for the primary safety outcome, a composite of major adverse cardiovascular events defined as cardiovascular death, myocardial infarction, or ischemic stroke.

WEIGHT MANAGEMENT

Weight loss can help overweight patients reach their hemoglobin A_1c target.

Metformin should be continued as other drugs are added because it does not induce weight gain and may help with weight loss of up to 2 kg as shown in the Diabetes Prevention Program Outcomes Study.¹⁹

GLP-1 receptor agonists and SGLT2 inhibitors help with weight loss and are good additions to a basal insulin regimen to minimize weight gain.

Liraglutide was associated with a mean weight loss of 2.3 kg over 36 months of treatment compared with placebo in the LEADER trial.¹⁰

In the Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6),²⁰ the mean body weight in the semaglutide group, compared with the placebo group, was 2.9 kg lower in the group receiving a lower dose and 4.3 kg lower in the group receiving a higher dose of the drug.

In a 24-week trial in 182 patients with type 2 diabetes inadequately controlled on metformin, dapagliflozin produced a statistically significant weight reduction of 2.08 kg (95% confidence interval 2.84–1.31; P < .0001) compared with placebo.²¹

Lifestyle changes aimed at weight management should be emphasized and discussed at every visit.

HYPOGLYCEMIA RISK

Hypoglycemia is a major consideration when tailoring hemoglobin A_1c targets. In the Action to Control Cardiovascular Risk (ACCORD) trial,²² severe, symptomatic hypoglycemia increased the risk of death in both the intensive and conventional treatment groups. In VADT, the occurrence of a recent severe hypoglycemic event was the strongest independent predictor of death within 90 days. Further analysis showed that even though serious hypoglycemia occurred more often in the intensive therapy group, it was associated with progression of coronary artery calcification in the standard therapy group.²³ Hence, it is imperative that tight glycemic control not be achieved at the cost of severe or recurrent hypoglycemia.

In terms of hypoglycemia, metformin is an excellent medication. The American Diabetes Association²⁴ recommends metformin as the first-line therapy for newly diagnosed diabetes. Long-term follow-up data from UKPDS showed that metformin decreased mortality and the incidence of myocardial infarction and lowered treatment costs as well as the overall risk of hypoglycemia.²⁵ When prescribed, it should be titrated to the highest dose.

The FDA²⁶ has changed the prescribing information for metformin in patients with renal impairment. Metformin should not be started if the eGFR is less than 45 mL/min/1.73 m², but it can be continued if the patient is already receiving it and the eGFR is between 30 and 45. Previously, creatinine levels were used to define renal impairment and suitability for metformin. This change has increased the number of patients who can benefit from this medication.

In patients who have a contraindication to metformin, DPP-4 inhibitors can be considered, as they carry a low risk of hypoglycemia as well. Sulfonylureas should be used with caution in these patients, especially if their oral intake is variable. When sulfonylureas were compared to the DPP-4 inhibitor sitagliptin as an add-on to metformin, the rate of hypoglycemia was 32% in the sulfonylurea group vs 5% in the sitagliptin group.²⁷

Of the sulfonylureas, glipizide and glimepiride are better than glyburide because of a comparatively lower risk of hypoglycemia and a higher selectivity for binding the K_ATP channel on the pancreatic beta cell.²⁸

Meglitinides can be a good option for patients who skip meals, but they are more expensive than other generic oral hypoglycemic agents and require multiple daily dosing.

GLP-1 analogues also have a low risk of hypoglycemia but are only available in injectable formulations. Patients must be willing and able to perform the injections themselves.²⁹

In 2010, among US residents age 65 and older, 10.9 million (about 27%) had diabetes,³⁰ and this number is projected to increase to 26.7 million by 2050.³¹ This population is prone to hypoglycemia when treated with insulin and sulfonylureas. An injury sustained by a fall induced by hypoglycemia can be life-altering. In addition, no randomized clinical trials show the effect of tight glycemic control on complications in older patients with diabetes because patients older than 80 are often excluded.

A reasonable goal suggested by the European Diabetes Working Party for Older People 2011³² and reiterated by the American Geriatrics Society in 2013³³ is a hemoglobin A_1c between 7% and 7.5% for relatively healthy older patients and 7.5% to 8% or 8.5% in frail elderly patients with diabetes.

Consider prescribing medications that carry a low risk of hypoglycemia, can be dose-adjusted for kidney function, and do not rely on manual dexterity for administration (ie, do not require patients to give themselves injections). These include metformin and DPP-4 inhibitors.

DRUG COMBINATIONS

Polypharmacy is a concern for all patients with diabetes, especially since it increases the risk of drug interactions and adverse effects, increases out-of-pocket costs, and decreases the likelihood that patients will remain adherent to their treatment regimen. The use of combination medications can reduce the number of pills or injections required, as well as copayments.

Due to concern for multiple drug-drug interactions (and also due to the progressive nature of diabetes), many people with type 2 diabetes are given insulin in lieu of pills to lower their blood glucose. In addition to premixed insulin combinations (such as combinations of neutral protamine Hagedorn and regular insulin or combinations of insulin analogues), long-acting basal insulins can now be prescribed with a GLP-1 drug in fixed-dose combinations such as insulin glargine plus lixisenatide and insulin degludec plus liraglutide.

COST CONSIDERATIONS

It is important to discuss medication cost with patients, because many newer diabetic drugs are expensive and add to the financial burden of patients already paying for multiple medications, such as antihypertensives and statins.

Metformin and sulfonylureas are less expensive alternatives for patients who cannot afford GLP-1 analogues or SGLT2 inhibitors. Even within the same drug class, the formulary-preferred drug may be cheaper than the nonformulary alternative. Thus, it is helpful to research formulary alternatives before discussing treatment regimens with patients.

When scientists discovered the band of hemoglobin A_1c during electrophoresis in the 1950s and 1960s and discerned it was elevated in patients with diabetes, little did they know the important role it would play in the diagnosis and treatment of diabetes in the decades to come.^1–3 Despite some caveats, a hemoglobin A_1c level of 6.5% or higher is diagnostic of diabetes across most populations, and hemoglobin A_1c goals ranging from 6.5% to 7.5% have been set for different subsets of patients depending on comorbidities, complications, risk of hypoglycemia, life expectancy, disease duration, patient preferences, and available resources.⁴

With a growing number of medications for diabetes—insulin in its various formulations and 11 other classes—hemoglobin A_1c targets can now be tailored to fit individual patient profiles. Although helping patients attain their glycemic goals is paramount, other factors should be considered when prescribing or changing a drug treatment regimen, such as cardiovascular risk reduction, weight control, avoidance of hypoglycemia, and minimizing out-of-pocket drug costs (Table 1).

CARDIOVASCULAR BENEFIT

Patients with type 2 diabetes have a 2 to 3 times higher risk of clinical atherosclerotic disease, according to 20 years of surveillance data from the Framingham cohort.⁵

Mixed results with intensive treatment

Reducing cardiovascular risk remains an important goal in diabetes management, but unfortunately, data from the long-term clinical trials aimed at reducing macrovascular risk with intensive glycemic management have been conflicting.

The United Kingdom Prospective Diabetes Study (UKPDS),⁶ which enrolled more than 4,000 patients with newly diagnosed type 2 diabetes, did not initially show a statistically significant difference in the incidence of myocardial infarction with intensive control vs conventional control, although intensive treatment did reduce the incidence of microvascular disease. However, 10 years after the trial ended, the incidence was 15% lower in the intensive-treatment group than in the conventional-treatment group, and the difference was statistically significant.⁷

A 10-year follow-up analysis of the Veterans Affairs Diabetes Trial (VADT)⁸ showed that patients who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1,000 person-years than those assigned to standard therapy, but no improvement in median overall survival. The hemoglobin A_1c levels achieved during the trial were 6.9% and 8.4%, respectively.

In 2008, the US Food and Drug Administration (FDA)⁹ mandated that all new applications for diabetes drugs must include cardiovascular outcome studies. Therefore, we now have data on the cardiovascular benefits of two antihyperglycemic drug classes—incretins and sodium-glucose cotransporter 2 (SGLT2) inhibitors, making them attractive medications to target both cardiac and glucose concerns.

Incretins

The incretin drugs comprise 2 classes, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors.

Liraglutide. The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial¹⁰ compared liraglutide (a GLP-1 receptor agonist) and placebo in 9,000 patients with diabetes who either had or were at high risk of cardiovascular disease. Patients in the liraglutide group had a lower risk of the primary composite end point of death from cardiovascular causes or the first episode of nonfatal (including silent) myocardial infarction or nonfatal stroke, and a lower risk of cardiovascular death, all-cause mortality, and microvascular events than those in the placebo group. The number of patients who would need to be treated to prevent 1 event in 3 years was 66 in the analysis of the primary outcome and 98 in the analysis of death from any cause.⁹

Lixisenatide. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial¹¹ studied the effect of the once-daily GLP-1 receptor agonist lixisenatide on cardiovascular outcomes in 6,000 patients with type 2 diabetes with a recent coronary event. In contrast to LEADER, ELIXA did not show a cardiovascular benefit over placebo.

Exenatide. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL)¹² assessed another GLP-1 extended-release drug, exenatide, in 14,000 patients, 73% of whom had established cardiovascular disease. In those patients, the drug had a modest benefit in terms of first occurrence of any component of the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (3-component major adverse cardiac event [MACE] outcome) in a time-to-event analysis, but the results were not statistically significant. However, the drug did significantly reduce all-cause mortality.

Semaglutide, another GLP-1 receptor agonist recently approved by the FDA, also showed benefit in patients who had cardiovascular disease or were at high risk, with significant reduction in the primary composite end point of death from cardiovascular causes or the first occurrence of nonfatal myocardial infarction (including silent) or nonfatal stroke.¹³

Dulaglutide, a newer GLP-1 drug, was associated with significantly reduced major adverse cardiovascular events (a composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in about 9,900 patients with diabetes, with a median follow-up of more than 5 years. Only 31% of the patients in the trial had established cardiovascular disease.¹⁴

Comment. GLP-1 drugs as a class are a good option for patients with diabetes who require weight loss, and liraglutide is now FDA-approved for reduction of cardiovascular events in patients with type 2 diabetes with established cardiovascular disease. However, other factors should be considered when prescribing these drugs: they have adverse gastrointestinal effects, the cardiovascular benefit was not a class effect, they are relatively expensive, and they must be injected. Also, they should not be prescribed concurrently with a DPP-4 inhibitor because they target the same pathway.

The other class of diabetes drugs that have shown cardiovascular benefit are the SGLT2 inhibitors.

Empagliflozin. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG)¹⁵ compared the efficacy of empagliflozin vs placebo in 7,000 patients with diabetes and cardiovascular disease and showed relative risk reductions of 38% in death from cardiovascular death, 31% in sudden death, and 35% in heart failure hospitalizations. Empagliflozin also showed benefit in terms of progression of kidney disease and occurrence of clinically relevant renal events in this population.¹⁶

Canagliflozin also has cardiovascular outcome data and showed significant benefit when compared with placebo in the primary outcome of the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, but no significant effects on cardiovascular death or all-cause mortality.¹⁷ Data from this trial also suggested a nonsignificant benefit of canagliflozin in decreasing progression of albuminuria and in the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate (eGFR), the need for renal replacement therapy, or death from renal causes.

The above data led to an additional indication from the FDA for empagliflozin—and recently, canagliflozin—to prevent cardiovascular death in patients with diabetes with established disease, but other factors should be considered when prescribing them. Patients taking canagliflozin showed a significantly increased risk of amputation. SGLT2 inhibitors as a class also increase the risk of genital infections in men and women; this is an important consideration since patients with diabetes complain of vaginal fungal and urinary tract infections even without the use of these drugs. A higher incidence of fractures with canagliflozin should also be considered when using these medications in elderly and osteoporosis-prone patients at high risk of falling.

Dapagliflozin, the third drug in this class, was associated with a lower rate of hospitalization for heart failure in about 17,160 patients—including 10,186 without atherosclerotic cardiovascular disease—who were followed for a median of 4.2 years.¹⁸ It did not show benefit for the primary safety outcome, a composite of major adverse cardiovascular events defined as cardiovascular death, myocardial infarction, or ischemic stroke.

WEIGHT MANAGEMENT

Weight loss can help overweight patients reach their hemoglobin A_1c target.

Metformin should be continued as other drugs are added because it does not induce weight gain and may help with weight loss of up to 2 kg as shown in the Diabetes Prevention Program Outcomes Study.¹⁹

GLP-1 receptor agonists and SGLT2 inhibitors help with weight loss and are good additions to a basal insulin regimen to minimize weight gain.

Liraglutide was associated with a mean weight loss of 2.3 kg over 36 months of treatment compared with placebo in the LEADER trial.¹⁰

In the Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6),²⁰ the mean body weight in the semaglutide group, compared with the placebo group, was 2.9 kg lower in the group receiving a lower dose and 4.3 kg lower in the group receiving a higher dose of the drug.

In a 24-week trial in 182 patients with type 2 diabetes inadequately controlled on metformin, dapagliflozin produced a statistically significant weight reduction of 2.08 kg (95% confidence interval 2.84–1.31; P < .0001) compared with placebo.²¹

Lifestyle changes aimed at weight management should be emphasized and discussed at every visit.

HYPOGLYCEMIA RISK

Hypoglycemia is a major consideration when tailoring hemoglobin A_1c targets. In the Action to Control Cardiovascular Risk (ACCORD) trial,²² severe, symptomatic hypoglycemia increased the risk of death in both the intensive and conventional treatment groups. In VADT, the occurrence of a recent severe hypoglycemic event was the strongest independent predictor of death within 90 days. Further analysis showed that even though serious hypoglycemia occurred more often in the intensive therapy group, it was associated with progression of coronary artery calcification in the standard therapy group.²³ Hence, it is imperative that tight glycemic control not be achieved at the cost of severe or recurrent hypoglycemia.

In terms of hypoglycemia, metformin is an excellent medication. The American Diabetes Association²⁴ recommends metformin as the first-line therapy for newly diagnosed diabetes. Long-term follow-up data from UKPDS showed that metformin decreased mortality and the incidence of myocardial infarction and lowered treatment costs as well as the overall risk of hypoglycemia.²⁵ When prescribed, it should be titrated to the highest dose.

The FDA²⁶ has changed the prescribing information for metformin in patients with renal impairment. Metformin should not be started if the eGFR is less than 45 mL/min/1.73 m², but it can be continued if the patient is already receiving it and the eGFR is between 30 and 45. Previously, creatinine levels were used to define renal impairment and suitability for metformin. This change has increased the number of patients who can benefit from this medication.

In patients who have a contraindication to metformin, DPP-4 inhibitors can be considered, as they carry a low risk of hypoglycemia as well. Sulfonylureas should be used with caution in these patients, especially if their oral intake is variable. When sulfonylureas were compared to the DPP-4 inhibitor sitagliptin as an add-on to metformin, the rate of hypoglycemia was 32% in the sulfonylurea group vs 5% in the sitagliptin group.²⁷

Of the sulfonylureas, glipizide and glimepiride are better than glyburide because of a comparatively lower risk of hypoglycemia and a higher selectivity for binding the K_ATP channel on the pancreatic beta cell.²⁸

Meglitinides can be a good option for patients who skip meals, but they are more expensive than other generic oral hypoglycemic agents and require multiple daily dosing.

GLP-1 analogues also have a low risk of hypoglycemia but are only available in injectable formulations. Patients must be willing and able to perform the injections themselves.²⁹

In 2010, among US residents age 65 and older, 10.9 million (about 27%) had diabetes,³⁰ and this number is projected to increase to 26.7 million by 2050.³¹ This population is prone to hypoglycemia when treated with insulin and sulfonylureas. An injury sustained by a fall induced by hypoglycemia can be life-altering. In addition, no randomized clinical trials show the effect of tight glycemic control on complications in older patients with diabetes because patients older than 80 are often excluded.

A reasonable goal suggested by the European Diabetes Working Party for Older People 2011³² and reiterated by the American Geriatrics Society in 2013³³ is a hemoglobin A_1c between 7% and 7.5% for relatively healthy older patients and 7.5% to 8% or 8.5% in frail elderly patients with diabetes.

Consider prescribing medications that carry a low risk of hypoglycemia, can be dose-adjusted for kidney function, and do not rely on manual dexterity for administration (ie, do not require patients to give themselves injections). These include metformin and DPP-4 inhibitors.

DRUG COMBINATIONS

Polypharmacy is a concern for all patients with diabetes, especially since it increases the risk of drug interactions and adverse effects, increases out-of-pocket costs, and decreases the likelihood that patients will remain adherent to their treatment regimen. The use of combination medications can reduce the number of pills or injections required, as well as copayments.

Due to concern for multiple drug-drug interactions (and also due to the progressive nature of diabetes), many people with type 2 diabetes are given insulin in lieu of pills to lower their blood glucose. In addition to premixed insulin combinations (such as combinations of neutral protamine Hagedorn and regular insulin or combinations of insulin analogues), long-acting basal insulins can now be prescribed with a GLP-1 drug in fixed-dose combinations such as insulin glargine plus lixisenatide and insulin degludec plus liraglutide.

COST CONSIDERATIONS

It is important to discuss medication cost with patients, because many newer diabetic drugs are expensive and add to the financial burden of patients already paying for multiple medications, such as antihypertensives and statins.

Metformin and sulfonylureas are less expensive alternatives for patients who cannot afford GLP-1 analogues or SGLT2 inhibitors. Even within the same drug class, the formulary-preferred drug may be cheaper than the nonformulary alternative. Thus, it is helpful to research formulary alternatives before discussing treatment regimens with patients.

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

PARIS – Treatment with the SGLT2 inhibitor dapagliflozin produced a statistically significant 27% drop in cardiovascular death or heart failure events in patients with existing heart failure with reduced ejection fraction and no diabetes, results that in a stroke changed the status of dapagliflozin from fundamentally a drug that treats diabetes to a drug that treats heart failure.

Mitchel L. Zoler/MDedge News

“Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction” (HFrEF), John McMurray, MD, said at the annual congress of the European Society of Cardiology.

The results he reported from the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial showed statistically significant benefits when adding dapagliflozin to guideline-directed therapy for a list of outcomes that include a 17% drop in all-cause death compared with placebo, an 18% fall in cardiovascular death, and a 25% relative reduction in total heart failure hospitalizations plus cardiovascular deaths during a median follow-up of just over 18 months. The primary endpoint of the reduction in cardiovascular death, first heart failure hospitalization, or an urgent heart failure visit fell by 25% in the enrolled patients with diabetes (45% of the study population, all with type 2 diabetes), and by 27% in the remaining patients who had no diabetes, showing that the presence of diabetes had no impact on the heart failure benefit from dapagliflozin (Farxiga). The absolute reduction in the primary endpoint was about 5%, with a number needed to treat of 21 to prevent one primary endpoint during 18 months of treatment.

Dr. McMurray’s report of the primary endpoint as well as the finding that the drug was as effective in patients without diabetes as in those with diabetes were both met with loud applause by the packed congress audience.

The efficacy results also showed that 58% of patients on dapagliflozin had a clinically meaningful (5 point or greater) increase in their quality of life score on the Kansas City Cardiomyopathy Questionnaire after 8 months on treatment compared with a 51% rate in the placebo patients, a statistically significant difference.

The safety results showed no new signals for a drug that already has regulatory approval but was being used in a novel population. The rate of major hypoglycemia was virtually nonexistent, 0.2%, and identical in both treatment arms. All adverse events occurred at roughly equal rates in the dapagliflozin and placebo groups, with a 5% rate of adverse events leading to study discontinuation in both arms, and a serious adverse event rate of 38% in the dapaglifolzin patients and 42% in the placebo patients. The rate of worsening renal function was less than 2% in both arms and not statistically different.

“This is as close to a home run as you see in heart failure treatment,” commented Douglas L. Mann, MD, professor of medicine at Washington University, St. Louis, and a heart failure clinician and researcher.

DAPA-HF “is a landmark trial. It took a diabetes drug and used it in patients without diabetes, a concept that would have been considered outlandish 5 years ago. Scientifically it’s huge,” commented Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston.

The DAPA-HF results were another step in the remarkable journey toward heart failure intervention taken by the SGLT2 (sodium glucose cotransport 2) inhibitor class of drugs that includes dapagliflozin as well as canagliflozin (Invokana) and empagliflozin(Jardiance), a path that began 4 years ago with the report of empagliflozin’s unexpected efficacy for reducing cardiovascular death and heart failure hospitalizations in a large cardiovascular-safety study, EMPA-REG OUTCOME (N Engl J Med. 2015 Nov 26;373[22]:2117-28). Subsequent reports showed similar effects benefiting heart failure and survival for canagliflozin and dapagliflozin, and now with DAPA-HF the evidence extended the benefit to heart failure patients regardless of whether they have diabetes. Additional studies now in progress are exploring the same question for empagliflozin and canagliflozin.

The results from DAPA-HF are likely a class effect for all these SGLT2 inhibitors, suggested Dr. McMurray in a video interview, a view shared by several other experts. He cautioned clinicians against using dapagliflozin to treat patients with heart failure with reduced ejection fraction (HFrEF) but without diabetes until this indication receives regulatory approval, and even then using dapagliflozin or other SGLT2 inhibitors this way may take some getting used to on the part of cardiologists and other clinicians.

“The results put dapagliflozin in the same league as [standard HFrEF drugs], but using it will require a shift in thinking. Most physicians will initially say “aren’t SGLT2 inhibitors used for treating diabetes?” Dr. Bhatt said.

“I’m sure most cardiologists are not familiar with the SGLT2 inhibitors; we’ll have to educate them,” conceded Dr. McMurray, professor of medical cardiology at the University of Glasgow. However, other aspects of dapagliflozin and this drug class in general may make the SGLT2 inhibitors particularly attractive and spur their use once labeling changes.

[email protected]

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA_1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m² or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA_1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

PARIS – Patients with stable coronary artery disease and type 2 diabetes saw fewer ischemic cardiovascular events when they received dual antiplatelet therapy with ticagrelor plus aspirin, though they also had more major bleeding events than patients receiving placebo plus aspirin.

The subset of patients who had received prior percutaneous coronary intervention (PCI) stood to benefit more from extended dual antiplatelet therapy (DAPT), according to clinical trial results presented to an overflow crowd at the annual congress of the European Society of Cardiology.

Findings from the full study, named The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS), and from the PCI subgroup analysis were published concurrently with the presentation (N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2).

“This strategy of long-term dual antiplatelet therapy may be beneficial in selected patients at low risk of bleeding, but at high risk of ischemic events,” said the study’s co-principal investigator Deepak Bhatt, MD, professor of medicine at Harvard Medical School, Boston, and executive director of interventional cardiology programs at Boston’s Brigham and Women’s Hospital. In a video interview, he hypothesized that “prior PCI may serve as a sort of ‘stress test’ for bleeding,” thus identifying a subset of patients who might benefit from long-term DAPT.

Ischemic events, the primary efficacy outcome of THEMIS, occurred in 7.7% of patients taking the P2Y12 receptor antagonist ticagrelor and 8.5% of those receiving placebo, for a hazard ratio of 0.90 favoring ticagrelor (P = .04). Ischemic events included cardiovascular deaths, myocardial infarctions (MIs), and stroke.

Looking at secondary endpoints, Dr. Bhatt said that there was no difference in cardiovascular deaths between study arms, but that ischemic strokes, all MIs, and ST segment elevation MIs were all less common for patients taking ticagrelor. All-cause mortality was similar between study groups.

Though ischemic events dropped, “This benefit was achieved at the expense of more bleeding,” said Dr. Bhatt. Major bleeding, the primary safety outcome, was seen in 2.2% of those taking ticagrelor and 1.0% of the placebo group, for a hazard ratio of 2.32 (P less than .001). Dr. Bhatt and his collaborators used the Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding for ascertainment of this outcome.

Intracranial hemorrhage was also more common for patients on ticagrelor, though incidence was low and the absolute difference was small between groups. This complication occurred in 0.7% of ticagrelor patients and 0.5% of placebo patients, yielding a hazard ratio of 1.71 (P = .0005). “This excess wasn’t in spontaneous or procedural intracranial bleeding, but rather in traumatic intracranial hemorrhage,” said Dr. Bhatt.

Fatal bleeds affected just 0.2% of those on ticagrelor and 0.1% of those receiving placebo; this difference wasn’t statistically significant.

koakes@mdedgecom

Source: Steg PG et al. N Engl J Med. 2019 Sep 1: DOI: 10.1056/NEJMoa1908077; Bhatt DL et al.Lancet. 2019 Sep 1: DOI:https://doi.org/10.1016/S0140-6736(19)31887-2)

Colorectal cancer (CRC) survivor rates are improving, which means people are living long enough after the cancer to have other chronic conditions. CRC is the third most commonly diagnosed cancer among users of the US Department of Veterans Affairs (VA) health care system, according to VA researchers, and there is a high prevalence of cardiovascular disease (CVD). The researchers also say emerging evidence suggests that survivors of CRC may be more likely to develop diabetes mellitus (DM) in the 5 years following their cancer diagnosis. But they add that there is a paucity of research about control of CVD-related chronic conditions among survivors of CRC.

In a retrospective study, the researchers compared 9,758 nonmetastatic patients with CRC with 29,066 people who had not had cancer. At baseline, 69% of the survivors of CRC and the matched controls were diagnosed with hypertension, 52% with hyperlipidemia, and 37% with DM.

But somewhat contrary to expectations, the researchers found no significant differences between the 2 groups for DM in the year following the baseline assessment. The researchers point to the VA’s “strong history” of DM risk reduction research and 2 national programs targeting DM, although they do not know whether the people in their study participated in those.

The survivors of CRC also had half the odds of being diagnosed with hyperlipidemia. However, they did have 57% higher odds of being diagnosed with hypertension.

Although the researchers acknowledge that hypertension is a transient adverse effect of certain chemotherapy regimens, they found only 7 survivors of CRC and 11 controls were treated with bevacizumab during their first year postanchor date.

The relationship between nonmetastatic CRC and CVD risk-related chronic conditions is complex, the researchers say. But they share risk factors, including obesity, physical inactivity, and diet.

The researchers call behavioral change interventions that improve survivors of CRC physical activity, dietary habits, and body mass index a “promising beginning” but call for other similar interventions, particularly those targeting blood pressure management and adherence to antihypertensive medications (which was significantly lower among the survivors).

While the magnitude of the effect regarding hypertension seems relatively small, the researchers say, they believe it is still an important difference when considered from a population health perspective—and one that should be addressed. The researchers also note that nonmetastatic survivors of CRC and controls had very similar rates of primary care visits in the 3 years postanchor date and as a result similar opportunities to receive a hypertension diagnosis.

Colorectal cancer (CRC) survivor rates are improving, which means people are living long enough after the cancer to have other chronic conditions. CRC is the third most commonly diagnosed cancer among users of the US Department of Veterans Affairs (VA) health care system, according to VA researchers, and there is a high prevalence of cardiovascular disease (CVD). The researchers also say emerging evidence suggests that survivors of CRC may be more likely to develop diabetes mellitus (DM) in the 5 years following their cancer diagnosis. But they add that there is a paucity of research about control of CVD-related chronic conditions among survivors of CRC.

In a retrospective study, the researchers compared 9,758 nonmetastatic patients with CRC with 29,066 people who had not had cancer. At baseline, 69% of the survivors of CRC and the matched controls were diagnosed with hypertension, 52% with hyperlipidemia, and 37% with DM.

But somewhat contrary to expectations, the researchers found no significant differences between the 2 groups for DM in the year following the baseline assessment. The researchers point to the VA’s “strong history” of DM risk reduction research and 2 national programs targeting DM, although they do not know whether the people in their study participated in those.

The survivors of CRC also had half the odds of being diagnosed with hyperlipidemia. However, they did have 57% higher odds of being diagnosed with hypertension.

Although the researchers acknowledge that hypertension is a transient adverse effect of certain chemotherapy regimens, they found only 7 survivors of CRC and 11 controls were treated with bevacizumab during their first year postanchor date.

The relationship between nonmetastatic CRC and CVD risk-related chronic conditions is complex, the researchers say. But they share risk factors, including obesity, physical inactivity, and diet.

The researchers call behavioral change interventions that improve survivors of CRC physical activity, dietary habits, and body mass index a “promising beginning” but call for other similar interventions, particularly those targeting blood pressure management and adherence to antihypertensive medications (which was significantly lower among the survivors).

While the magnitude of the effect regarding hypertension seems relatively small, the researchers say, they believe it is still an important difference when considered from a population health perspective—and one that should be addressed. The researchers also note that nonmetastatic survivors of CRC and controls had very similar rates of primary care visits in the 3 years postanchor date and as a result similar opportunities to receive a hypertension diagnosis.

Colorectal cancer (CRC) survivor rates are improving, which means people are living long enough after the cancer to have other chronic conditions. CRC is the third most commonly diagnosed cancer among users of the US Department of Veterans Affairs (VA) health care system, according to VA researchers, and there is a high prevalence of cardiovascular disease (CVD). The researchers also say emerging evidence suggests that survivors of CRC may be more likely to develop diabetes mellitus (DM) in the 5 years following their cancer diagnosis. But they add that there is a paucity of research about control of CVD-related chronic conditions among survivors of CRC.

In a retrospective study, the researchers compared 9,758 nonmetastatic patients with CRC with 29,066 people who had not had cancer. At baseline, 69% of the survivors of CRC and the matched controls were diagnosed with hypertension, 52% with hyperlipidemia, and 37% with DM.

But somewhat contrary to expectations, the researchers found no significant differences between the 2 groups for DM in the year following the baseline assessment. The researchers point to the VA’s “strong history” of DM risk reduction research and 2 national programs targeting DM, although they do not know whether the people in their study participated in those.

The survivors of CRC also had half the odds of being diagnosed with hyperlipidemia. However, they did have 57% higher odds of being diagnosed with hypertension.

Although the researchers acknowledge that hypertension is a transient adverse effect of certain chemotherapy regimens, they found only 7 survivors of CRC and 11 controls were treated with bevacizumab during their first year postanchor date.

The relationship between nonmetastatic CRC and CVD risk-related chronic conditions is complex, the researchers say. But they share risk factors, including obesity, physical inactivity, and diet.

The researchers call behavioral change interventions that improve survivors of CRC physical activity, dietary habits, and body mass index a “promising beginning” but call for other similar interventions, particularly those targeting blood pressure management and adherence to antihypertensive medications (which was significantly lower among the survivors).

While the magnitude of the effect regarding hypertension seems relatively small, the researchers say, they believe it is still an important difference when considered from a population health perspective—and one that should be addressed. The researchers also note that nonmetastatic survivors of CRC and controls had very similar rates of primary care visits in the 3 years postanchor date and as a result similar opportunities to receive a hypertension diagnosis.

Postmenopausal women with a first-degree family history of diabetes (FHD) had higher bone mineral density (BMD) than did those without such a history, according to results of a study.

Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm², respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm², respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.

Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).

“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.

The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.

The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.

[email protected]

SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.

Postmenopausal women with a first-degree family history of diabetes (FHD) had higher bone mineral density (BMD) than did those without such a history, according to results of a study.

Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm², respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm², respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.

Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).

“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.

The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.

The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.

[email protected]

SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.

Postmenopausal women with a first-degree family history of diabetes (FHD) had higher bone mineral density (BMD) than did those without such a history, according to results of a study.

Lijuan Yang, MD, of First Affiliated Hospital of Wenzhou (China) Medical University and colleagues reported the results in Menopause. The cross-sectional study included 892 normoglycemic postmenopausal women, of whom 147 had a first-degree FHD; the mean age was 55 years among both those with and those without first-degree FHD. The investigators assessed BMDs of the femoral neck and lumbar spine with dual-energy x-ray absorptiometry and insulin resistance with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).

Lumbar spine BMD was higher in those with first-degree FHD than in those without, at 1.077 and 1.034 g/cm², respectively; femoral neck BMD was similarly higher at 0.89 vs. 0.85 g/cm², respectively. HOMA-IR also was higher among those with first-degree FHD than among those without, at 1.85 and 1.60, respectively.

Spearman’s correlation analyses showed that lumbar spine BMD was positively associated with first-degree FHD (P = .008) and HOMA-IR (P = .041), as was femoral neck BMD (P = .013 and P = .005, respectively). Results of multiple stepwise regression analysis showed that first-degree FHD and HOMA-IR were independent factors positively associated with femoral neck BMD (P = .029 and P = .0009, respectively) and lumbar spine BMD (P = .029 and P = .002).

“The present study demonstrated that lumbar spine BMD and femoral neck BMD were positively associated with HOMA-IR in postmenopausal women and that individuals with a first-degree FHD were more likely to have high HOMA-IR,” the investigators said. “We suggest that the elevated BMD in individuals with a first-degree FHD could be attributed to insulin resistance,” which appears to be inherited by persons with a first-degree FHD.

The authors noted that the cross-sectional design is a limitations of this study. They suggested future studies might investigate the relationship between insulin resistance and bone development in these populations by assessing osteocalcin and P1NP.

The study received funding or support from National Key R&D Program of China and from the Wenzhou Science & Technology Bureau. The authors did not disclose any conflicts of interest.

[email protected]

SOURCE: Yang L et al. Menopause. 2019 Aug 19. doi: 10.1097/GME.0000000000001396.

The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

[email protected]

The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

[email protected]

The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

[email protected]

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

Innovations in care delivery, as previously introduced by Dr. Robert Gabbay, can enhance the patient and physician experience. Providing care via telemedicine can bring joy to work by introducing variety to practice. It also carries the satisfaction of easing access to care for the patient.

Vanderbilt University Medical Center

Broadly speaking, telemedicine can be seen as a tool for delivering care when a hands-on exam is not required. In direct-to-patient telemedicine, the patient can use a personal smartphone, tablet, or computer to connect with a provider in a real-time audio and/or video “visit” from home or work. The engagement can be scheduled or on demand. Although telemedicine is generally associated with the delivery of care to patients in remote or rural locations, it is increasingly being used in urban areas, especially with older patients and those for whom transport or time away from work might be difficult.
 

How the patient benefits

This built-in flexibility is appealing to patients – the easier access and convenience can translate into reduced time away from work or school and possibly a reduction in patient “no-shows.” Patients are more likely to enjoy the benefits of continuity of care with their own providers, rather than seeking independent, consumer-marketed services. In a nationwide survey of 4,345 respondents about attitudes toward telemedicine in primary care, 52% of respondents said they would like to see their own providers via telemedicine, 35% were willing to see a different provider from the same organization, and 15% said they would consider leaving their current provider to see one who offered telemedicine (BMC Health Services Research. 2017;17:784).

In addition, numerous studies have reported on the equivalent clinical outcomes and improved cost-of-care benefits in patients who receive diabetes care through telemedicine. Lui and colleagues looked at patients at the Denver VA Medical Center who were newly diagnosed with diabetes and they compared short-term glycemic control in patients who had telemedicine consultations with patients who had in-person visits. They found that the telemedicine consultations improved short-term glycemic control as effectively as the in-person visits, but with possible added financial benefits for both the patients and the health care system. (J Diabetes Sci Technol. 2016;10[5]:1079-86). Likewise, Fatehi and colleagues have reported that method of consultation – telemedicine or in-person consultation – did not affect concordance of advice between two endocrinologists (Diabetes Technol Ther. 2015;17[10]:717-25).
 

What telemedicine has to offer

There is a range of diabetes care services that can be delivered through telemedicine consultation. When appropriate diagnostic labs have already been performed, newly diagnosed patients can be counseled on their diagnosis and started on therapy. For patients who have already been diagnosed, follow-up and monitoring of therapy adherence and glycemic control can be more convenient and done more routinely, compared with in-person visits, and thus yield better outcomes.

Use of cloud-based services to review data from glucometers, insulin pumps, and continuous glucose monitors allows the clinicians to access the same data they would in the office. Combining this data review with a video visit, rather than looking at the data in isolation, allows for increased patient engagement, shared decision making, and patient counseling.

Other diagnoses that readily fit at-home telemedicine care include gestational diabetes, as these patients need frequent follow-up, and doing some of their visits via telemedicine can reduce their burden of travel. Hypothyroidism follow-ups, with labs completed before the visit, can be very efficient via telemedicine. Internal surveys of direct-to-patient services at my institution demonstrated a high level of patient satisfaction, with 91% of patients indicating they were satisfied overall, and 81% saying that connection with the provider matched that of an in-person visit.
 

Gains for the provider, the care team, and the practice

Endocrinologists can derive benefit from telemedicine engagement with their patients, which could have positive implications for other members of the care team and for the practice as a whole. For the provider, being able to streamline clinical workflows and increase practice efficiency can help reduce personal and workplace-related stress and translate into greater personal satisfaction in one’s work and delivery of better-quality care.

At the practice level, the use of telemedicine presents opportunities for expanding the patient base and perhaps working more flexible hours to better accommodate the personal and professional time demands on providers and their staff. In addition, offering telemedicine as a medium of consultation could be a practice differentiator that could give you a competitive edge. That, along with smaller changes, such as enhancing or even reducing space utilization, could contribute to reduced overheads and a boost in revenue, which would have a positive impact on the practice’s bottom line.
 

Getting started

There is important groundwork to be done before a telemedicine program can get underway. First, bear in mind that there is considerable state-based variation in regulations and insurance coverage, so you need to be sure that you are in compliance with the requirements for your state. If direct-to-patient telemedicine is not widely reimbursed in your state, direct-payment models may be feasible. Providers who accept Medicare payments need to understand restrictions on self-payment for those patients. You may also be able to negotiate with payers to include reimbursement for telemedicine visits in your contracts. Negotiation with payers and direct-pay models may be possible.

Key guidelines. In addition to understanding your state’s regulations around telemedicine, there are specific aspects of practice about which you need to be clear, for example:

• You must be licensed in the state in which your patient is located at the time of their visit.
• Understand any restrictions on prescribing via telemedicine in your state.
• Be aware that Medicare has very specific guidelines and, at this time, does not recognize home as a place of service.
• You must be sure that you use HIPAA-compliant video software.
• If in any doubt, seek guidance from an attorney or your organization’s compliance office.

Infrastructure and outlay. Your infrastructure needs will depend on the specific services that you provide, but in general, you should include a communication platform and video conferencing equipment; sufficient bandwidth and a secure, reliable Internet connection; ready access to sound IT support; and comprehensive staff training at the outset, with subsequent refresher training sessions on a regular basis. Within the practice, you will need to think about adjustments to your existing workflow to accommodate the telemedicine services you plan to offer.

Resources. Two nonprofit groups that offer nonpartisan guidance in telemedicine are the Center for Connected Health Policy and the Regional Telehealth Resource Centers.

Dr. Griffith is assistant professor of medicine and medical director, Ambulatory Telehealth Services, Vanderbilt University Medical Center, in Nashville, Tenn. This article is part of a series based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Griffith has no disclosures. Write to her at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

There is a national epidemic of physician burnout, and endocrinologists are not immune to it, with 47% reporting significant burnout in a recent survey.¹ As the incidence of physician burnout increases, so does the overall cost to the health system, both in quality of care and financially, and findings from a recent study suggested that patients are becoming aware of burnout among providers and are concerned about its impact on the quality of the care that they are receiving.²

Burnout can be described as a form of extreme work-related stress manifesting as physical and/or emotional exhaustion that can generate a range of psychological ripple effects, such as depression, mood and anxiety disorders, a crippling sense of worthlessness, and a loss of sense of self. Anyone can be affected by burnout, but there seems to be a greater prevalence among women (50% vs 30% for men); younger doctors, especially residents; and providers of color.^3,4

The fallout from burnout affects both our personal and professional lives. In our personal lives, it can translate into broken or strained relationships, alcohol and substance abuse, depression and mood or anxiety disorders, financial difficulties, and suicide (14% have reported thoughts of suicide; 1% have committed suicide). Juggling work and family can be overwhelming, and additional strains, such as caring for a parent or a sick family member, having a child, going through a divorce or a family bereavement, dealing with student debt, and pressure to achieve, can be cumulatively devastating for a hardworking provider.⁵

In the practice, we see burnout translate into an increase in the number of medical errors, diminished quality of care, lower patient satisfaction with care, decreased productivity and professional effort, dissatisfaction among staff, and an increase in physician turnover.⁶ Workplace-specific factors that can contribute to burnout include daily use of health information technology, especially the EHR; workplace inequities; pressures to keep abreast with changes in the specialty; and time management challenges and constraints that go along with the continual pressure to deliver better quality care, for less money, in less time.⁷

Our group wanted to devise innovative, practice-based strategies that would help our colleagues address the burnout crisis. We asked ourselves how – through new, innovative models of care – we could rediscover the joy in our work, and what the steppingstones of “meaningful work” would be. It seemed to us that working as a team and revisiting the care we deliver might be good starting points, and that, if we drilled down further, common themes to address burnout and find joy in work revolve around choice, camaraderie, equity, and cocreating solutions.

Evidence suggests that physicians who spend at least 20% of their professional effort focused on work they find most meaningful have a notably lower risk for burnout.⁸ Each 1% reduction below this threshold increases the risk of burnout, and there is a ceiling effect to the benefit at 20% – for example, spending 50% of your time in the most meaningful area is associated with similar rates of burnout as spending 20% on it.

So how do we to get to that meaningful threshold of 20%? You can begin with identifying your passion, making the business case, speaking to your boss, getting your colleagues’ buy-in, and even looking for grants and other funding if needed. We came up with five ways you might bring more joy to your work by adopting innovative models of diabetes care: the first – implementing a direct-to-patient telemedicine program – has been written by Michelle Griffith, MD, and is featured here. In coming articles, we will take a look at tackling the impediments of clinical inertia, coordinating care through use of a transfer summary, shifting to team-based care, how to use  e-consultations to connect with primary care providers, and devising a business case for these and other innovations.

References

1. Kane L. National Physician Burnout, Depression & Suicide Report 2019. Medscape. Published online Jan 16, 2019.

2. American Society of Health-System Pharmacists. Press release. 2019 Jun 17.

3. Oakes K. Female family physicians come up short in burnout gender divide. Family Practice News. Published online November 27, 2017.

4. Dyrbye L. JAMA Network Open. 2019 Jul 26. doi: 10.1001/jamanetworkopen.2019.7457.

5. Yank V et al. JAMA Intern Med. 2019 Jan 28. doi: 10.1001/jamainternmed.2018.6411.

6 . Panagioti M et al. JAMA Intern Med. 2018;178(10):1317-31.

7. Gardner R et al. J Am Med Inform Assoc. doi: 10.1093/jamia/ocy145.

8. Shanafelt T et al. Am J Med Qual. 2017;32(5):563-5.

Dr. Gabbay is chief medical officer at Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School, both in Boston. This is the introduction to a series of articles based on presentations from the annual meeting of the Endocrine Society in March 2019. Dr. Gabbay reports being an adviser to Lark, Onduo, and HealthReveal. Write to him at [email protected].

The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

©wildpixel/Thinkstock

In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.

The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

©wildpixel/Thinkstock

In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.

The fracture risk assessment tool FRAX may underestimate fracture risk in women with diabetes when bone mineral density is included, according to data from 566 women aged 40-90 years.

©wildpixel/Thinkstock

In a study published in Bone Reports, Lelia L.F. de Abreu, MD, of Deakin University, Geelong, Australia, and colleagues investigated the accuracy of FRAX scores and the role of impaired fasting glucose (IFG) and bone mineral density (BMD) on fracture risk by comparing FRAX scores for 252 normoglycemic women, 247 women with IFG, and 67 women with diabetes.

When BMD was not included, women with diabetes had a higher median FRAX score for major osteoporotic fractures of the hip, clinical spine, forearm, and wrist than women without diabetes or women with IFG (7.1, 4.3, and 5.1, respectively). In the diabetes group, 11 major osteoporotic fractures were observed versus 5 predicted by FRAX. In the normoglycemic group, 28 fractures were observed versus 15 predicted, and in the IFG group 31 fractures were observed versus 16 predicted.

When BMD was included, major osteoporotic fractures and hip fractures also were underestimated in the diabetes group (11 observed vs. 4 observed; 6 observed vs. 1 predicted, respectively), but the difference in observed versus predicted fractures trended toward statistical significance but was not significant (P = .055; P = .52, respectively). FRAX with BMD increased the underestimation of major osteoporotic fractures in the normoglycemic and IFG groups (28 observed vs. 13 predicted; 31 observed vs. 13 predicted).

The study findings were limited by several factors including the inability to determine the impact of specific types of diabetes on fracture risk, lack of data on the duration of diabetes in study participants, the use of self-reports, and a relatively small and homogeneous sample size, the researchers noted.

However, the results support data from previous studies showing an increased fracture risk in diabetes patients regardless of BMD, and suggest that FRAX may be unreliable as a predictor of fractures in the diabetes population, they concluded.

The study was supported in part by the Victorian Health Promotion Foundation, National Health and Medical Research Council Australia, and the Geelong Region Medical Research Foundation. Two researchers were supported by university postgraduate rewards and one researcher was supported by a university postdoctoral research fellowship. The remaining coauthors reported no relevant financial conflicts.

SOURCE: de Abreu LLF et al. Bone Reports. 2019 Aug 13. doi: 10.1016/j.bonr.2019.100223.