Diabetes

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

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

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

How much does the risk of new-onset type 2 diabetes (T2D) increase in patients who have had a mild SARS-CoV-2 (COVID-19) infection?

Dr. Jain: We are now finding many associations between COVID-19 and T2D. Recently, there have been studies, especially from the United States and Germany, showing that even after mild COVID-19, the occurrence of new onset T2D is greater than what we thought previously. For instance, we are now seeing that the rate of new-onset T2D in adults who have had mild COVID-19 is about 18 additional adults per 1000 people. These people have about a 46% higher risk of developing T2D compared to those who did not have COVID-19. This is something we must keep in mind moving forward when it comes to screening for diabetes.

How have you navigated through the diagnostic components of T2D and COVID-19?

Dr. Jain: When people were exclusively doing virtual appointments during the COVID-19 lockdowns, there wasn't enough screening for retinopathy, worsening blood pressure, or even basic lab testing, for instance. We could not perform electrocardiography screenings for our patients with diabetes; we had to defer it unless people were symptomatic. This was not the ideal situation, as many people with diabetes may have “silent” coronary artery disease, making screening crucial even in those patients who are not symptomatic. The impact of this is anyone’s guess at this time. Unfortunately, there is no literature that has looked at the impact of deferred screenings during the pandemic.

However, in my own practice, we are now transitioning back to in-person appointments and making sure that all of these screening visits are being conducted in a timely manner so that we can catch the micro- and macrovascular complications of diabetes sooner.

Although data on the long-term impact are not available, what studies have been done regarding the treatment of T2D during the pandemic?

Dr. Jain: There are some observational studies. There was a claims database analysis that looked at patient visits, screening tests, filling of medications, and glycated hemoglobin (A1C) levels in 2020 vs 2019 in the United States. There was no significant difference between the A1C levels and medication fills. I think one reason for this is that we all were able to adapt to the changes required from us, and we were able to incorporate the virtual appointments. That's reassuring. I think we still need some more data to make any definitive assumptions about what the overall care of diabetes has been as we are coming out of the pandemic.

Have you seen any particular characteristics or disparities in those patients who have been impacted by T2D and COVID-19?

Dr. Jain: With the mask mandate, physical distancing requirements, and differing vaccination rates across parts of the world, we have seen disparities in the impact of COVID-19, especially for those that are the most vulnerable. This includes people with multiple comorbidities.

We also know that, even at baseline, patients with T2D are often prone to multiple cardiovascular issues and dialysis requirements. These individuals still have to be extremely cautious. I have seen that those patients who actually need the most attention are still not able to go out and get the care. It is important that we are inclusive in our understanding of the requirements of people at high risk for T2D and other comorbidities. Necessary requirements to reduce infection risk include following physical distancing and masking requirements as appropriate and ensuring timely screening for retinopathy, nephropathy, and coronary artery disease as well as getting foot exams.

We have to give them all the care and access to healthcare that they need. Expert consensus suggests that we ensure optimization of vaccination status, glycemic control, cardiovascular risk, and weight control. We also need to ensure that these high-risk individuals have not slipped through the cracks and have appropriate appointment follow-ups, labs, etc. booked in a timely manner.

What guidelines and standards do you rely upon to ensure that patients are getting the most out of their treatment?

Dr. Jain: COVID-19 aside, we still want to make sure that the management of T2D is not glucose-centric. We now understand that diabetes requires 360-degree care, and that involves not only controlling the blood sugars but also making sure that we are mitigating risk factors for vascular complications. That includes ensuring blood pressure is well controlled and that cholesterol levels are in target range for patients who either have history of heart attacks, strokes, heart failure, kidney disease, or who are at future risk for these events.

We are using medications that can help protect the heart and the kidneys. Considering that T2D and obesity are so closely interlinked, we are using medications that help with overcoming the weight aspect as well. I think that a patient-centric, multidisciplinary approach is the most crucial and the most reliable way of getting that 360-degree comprehensive care for patients with diabetes.

Is there anything else you would like to share with your colleagues or peers?

Dr. Jain: As we are coming out of the pandemic, we still we need to realize that the repercussions of COVID-19 will still stay with us for a long, long time. We do know that COVID-19 infection leads to a tsunami of inflammation in the body. This can have long-lasting effects, including chronic conditions.

It is important that we continue to screen for diabetes given that there is a higher incidence of T2D in those with even mild COVID-19, and especially those at highest risk, such as people with obesity. We need to make sure that we are not missing any pieces of the puzzle there, especially because diabetes is a silent disease. We should not rely on symptoms to determine when we should screen; instead, we must be proactive about screening and management.

This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

This transcript has been edited for clarity.

Today, I’m going to discuss the results of a new automated insulin delivery system that I think can really help many people with type 1 diabetes.

Dr. Steven Russell presented the results at the Advanced Technologies & Treatments for Diabetes meeting. The study focused on the iLet system, which is made by Beta Bionics and has been under development for a while. This was the single-hormone study, so it just looked at their algorithm using insulin alone. Eventually they’re going to study this, looking at the use of insulin plus glucagon together to see if that further improves outcomes.

One of the main reasons I think this study was so cool is because it included over 25% minority individuals who aren’t routinely studied in these insulin device trials. The study also included people who had a wide range of hemoglobin A1c levels; there was no high cut-point here. Over 30% of participants had an A1c greater than 8%. They also studied both children and adults and combined the results together.

Before I talk about the results, let me tell you about the pump. This is a tubed pump that has a sensor that it communicates with – it’s the Dexcom sensor – and it has an algorithm so it does automated insulin delivery. Instead of having to enter all sorts of information into the system, this thing requires that you put in only the patient’s weight. That’s it. From there, the system begins to figure out what the patient needs in terms of automated insulin delivery.

There are several different target settings that can be entered, and they can differ by time of day. There’s basically the time of day that one is eating a meal, so breakfast, lunch, or dinner, and there is the meal size, basically small, medium, and large. The individual enters this in real time so the system knows they’re eating, but other than that, the system just works.

It does this in a way that doesn’t allow for the individual using the pump to fidget with it. They can’t override the system and they can’t put in other insulin doses. The system is just there to take care of their diabetes.

They compared this system with people on any other system, including other automated insulin delivery systems, and put them into this trial. People were randomized to this system vs. whatever they’d been on (that was the control group) and they followed them for 13 weeks, which is not all that long.

There was a 0.5% reduction in A1c between the two groups. There was also an increase in the time in range, and this improvement in time in range happened almost immediately – within the first day or two of people being on the system. In terms of actual numbers, the adult patients started out with a time in range of 56% and this increased to 69% by the end of the study. The biggest improvement was time in range overnight, as is seen with other automated insulin delivery systems.

There was no reduction in time below a glucose level of 54 and there was an increase in the number of episodes of severe hypoglycemia in the group treated with the iLet system, but this was not statistically significant between the two groups.

I think these results are hard to compare with other pivotal trials investigating automated insulin delivery systems. The Tandem pivotal trial was a randomized controlled trial similar to this one, but the Medtronic and Omnipod studies were single-arm trials where patients were compared before and after they used the device.

More than anything, I think what’s important about this system is that it may allow for greater use of automated insulin delivery systems. It may allow primary care providers to use these systems without needing all sorts of support, and patients may be able to use these devices more simply than a device where they have to do carb counting and adjusting in ways that I think tend to be pretty complicated and require higher numeracy and literacy skills.

I couldn’t be happier. I love what they’re doing at Beta Bionics, and I look forward to more results, and in particular, to see if these results improve further when they do a study of insulin and glucagon in their dual-hormone pump system.

Thank you very much. This has been Dr Anne Peters for Medscape.
 

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen.

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

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Monocyte-lymphocyte ratio (MLR) was significantly associated with proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes (T2D).

Major finding: Each 0.1 unit increase in MLR increased the risk for PDR by 46% (adjusted odds ratio 1.46; P = .014), with the effects being stable across different subgroups stratified by age, sex, hemoglobin, and glycated hemoglobin categories.

Study details: Findings are from a cross-sectional study of 367 patients with T2D and diabetic retinopathy, of which 27% were diagnosed with PDR.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Wang H et al. Association of monocyte-lymphocyte ratio and proliferative diabetic retinopathy in the U.S. population with type 2 diabetes. J Transl Med. 2022;20:219 (May 13). Doi: 10.1186/s12967-022-03425-4

Key clinical point: Monocyte-lymphocyte ratio (MLR) was significantly associated with proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes (T2D).

Major finding: Each 0.1 unit increase in MLR increased the risk for PDR by 46% (adjusted odds ratio 1.46; P = .014), with the effects being stable across different subgroups stratified by age, sex, hemoglobin, and glycated hemoglobin categories.

Study details: Findings are from a cross-sectional study of 367 patients with T2D and diabetic retinopathy, of which 27% were diagnosed with PDR.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Wang H et al. Association of monocyte-lymphocyte ratio and proliferative diabetic retinopathy in the U.S. population with type 2 diabetes. J Transl Med. 2022;20:219 (May 13). Doi: 10.1186/s12967-022-03425-4

Key clinical point: Monocyte-lymphocyte ratio (MLR) was significantly associated with proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes (T2D).

Major finding: Each 0.1 unit increase in MLR increased the risk for PDR by 46% (adjusted odds ratio 1.46; P = .014), with the effects being stable across different subgroups stratified by age, sex, hemoglobin, and glycated hemoglobin categories.

Study details: Findings are from a cross-sectional study of 367 patients with T2D and diabetic retinopathy, of which 27% were diagnosed with PDR.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Wang H et al. Association of monocyte-lymphocyte ratio and proliferative diabetic retinopathy in the U.S. population with type 2 diabetes. J Transl Med. 2022;20:219 (May 13). Doi: 10.1186/s12967-022-03425-4

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] −0.36%; P = .008, and ETD −0.4%; P = .003, respectively) and body weight (ETD −3.15 and −5.15 kg, respectively; both P < .001).

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4