The evolution of SGLT2 inhibitors from an agent known for mild reductions in HbA1c and body weight to a therapy with proven cardiovascular and renal benefits has captured the attention of endocrinologists, cardiologists, nephrologists, and even primary care providers. What were once trends and observational results have now been confirmed by landmark clinical trials. It seems every major cardiology or diabetes conference in the past few years have been headlined by such a trial and it is hard to see that trend ending any time soon—especially with so many unanswered questions remaining related to the mechanism of actions behind these therapies.


The most recent of these presentations was given by David Cherney, MD, PhD, associate professor in the departments of Medicine and Pharmacology and Toxicology at the University of Toronto, when he presented an analysis of VERTIS-CV examining the renal outcomes with use of ertugliflozin (Steglatro) in the cardiovascular outcomes trial. While the trial demonstrated the benefits of ertugliflozin on renal function in the study population, 

reached out to Cherney to learn more about the implications of this trial.

In the following interview, Cherney offers his perspective on what specialists bare the responsibility of prescribing these agents to patients for whom they are appropriate and to learn more about why multiple fields being knowledgable of SGLT2 inhibitors will improve the care of patients.

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An associate professor from University of Toronto discusses whose responsibility it is to prescribe SGLT2 inhibitors to patients.

David Cherney, MD: SGLT2 Inhibitors and Prescribing Responsibility

New data from a team of investigators in Taiwan is underlining the importance of physical activity and exercise for long-term survival in patients with type 2 diabetes.

Presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, the analysis of more than 4500 patients over a 15-year period suggests greater levels of exercise was linked to a 25-32% reduction in risk of all-cause mortality among patients with type 2 diabetes.

"Among people with type 2 diabetes, those with increased exercise capacity had a significantly decreased risk of all-cause mortality. Further studies should investigate the type and dose of exercise that is most helpful to promote health and prolong life expectancy,” wrote study investigators.

While many studies have examined the effects of exercise in diabetics, investigators noted few had examined associations between exercise capacity and all-cause mortality. To provide further information on this subject, investigators from the Taichung Veterans General Hospital in Taiwan designed their study as an analysis of data from the National Health Interview Survey (NHIS) and the National Health Insurance research databases.

As part of NHIS, patients underwent standardized face-to-face interviews in 2001, 2005, 2009, and 2013. Through a search of the National Health Insurance research database from 2000-2016, investigators were able to confirm comorbidities for each patient and, from the National Registration of Death, investigators were able to ascertain instances of mortality.

Investigators identified a total of 4859 adult participants with type 2 diabetes for their study. Of these, 49.15% (n=2389) were men and the cohort had a mean age of 59.5 (12.63) years. Using Kaplan-Meier curves, of all-cause mortality stratified by exercise capacity, investigators unveiled significant findings. In univariate Cox regression analysis, investigators found those with higher exercise capacity had a significantly decreased risk of all-cause mortality compared to those with no exercise habits (moderate exercise with 0-800 kcal/week HR, 0.83; 95% CI, 0.71-0.97, high exercise with more than 800 kcal/week HR, 0.77; 95% CI, 0.67-0.89).

After adjustment for potential confounders, a multivariate Cox regression analysis indicated those with a higher exercise capacity was associated with a significantly decreased risk of all-cause mortality compared to those with no exercise habits (moderate exercise with 0-800 kcal/week: HR, 0.75, 95% CI: 0.62-0.91, high exercise with more than 800 kcal/week: HR, 0.68, 95% CI, 0.57-0.81). Additionally, investigators noted a significant trend (

In a sensitivity analysis excluding mortality in the first and second year in the study period, results suggest those with increased exercise capacity had a significantly decreased risk of all-cause mortality.

Association between exercise capacity and all-cause mortality in people with type 2 diabetes

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A study presented at EASD 2020 examines the impact of increased exercise capacity on risk of all-cause mortality among more than 4k patients with type 2 diabetes.

Study Finds Increased Exercise Lowers Mortality Risk 25-32% Among Diabetics

While most studies related to coronavirus disease 2019 (COVID-19) and diabetes focused on increased risk of mortality, new data suggest stay-at-home orders and spending time in lockdown may have improved diabetes management for those with 

European Association for the Study of Diabetes (EASD) 2020 Annual Meeting

, results of the Italian study indicate patients with type 1 diabetes who stopped working achieved greater glycemic control during the lockdown than they had before the lockdown began.

“Despite the psychological stress and very limited opportunities for exercise, the study found that glucose control was significantly improved in patients with T1D who stayed at home during the first week of the COVID-19-induced lockdown in Italy. This observation suggests that slowing down routine activities can have beneficial effects on T1D control in the short term,” wrote investigators.

With the COVID-19 pandemic presenting clinicians and patients with a slew of new hurdles in disease management, a team from University Hospital of Padova wanted to develop a greater understanding of how changes as a result of the pandemic impacted glycemic control. With this in mind, they designed their study to as a retrospective analysis of patients with type 1 diabetes using a flash glucose monitoring device.

For inclusion in the study, patients had to meet the following criteria: attend the diabetes clinic at the University Hospital of Padova, live in the nearby area, use the FreeStyle Libre FGM system for at least 3 months, share sensor data with the outpatient clinic, and have greater than 90% coverage of sensor data. From the sensor data, investigators hoped to obtain data related to average glucose, standard deviation, and percentage time in hypoglycemia, glucose range, and hyperglycemia.

For the purpose of analysis, hypoglycemia was defined as less than 70 mg/dl, glucose range was defined as 70-180 mg/dl, and hyperglycemia was defined as greater than 180 mg/dl. In total, 33 individuals were identified for inclusion, of which 20 had stopped working and were included in the final analysis. In comparison, those who stopped working were more likely to be younger, male, and have a greater length of diabetes duration.

Upon analysis, investigators found the average glucose declined from 177±45 mg/dl during the week before the lockdown to 160±40 mg/dl during the lockdown (

=.005). Additionally, results indicated time in range increased from 54.5% before the lockdown to 65.2% during the lockdown while time in hyperglycemia decreased from 42.3% before the lockdown to 31.6% during the lockdown (

Investigators also pointed out none of the measurements of glycemic control changed during the lockdown for the 13 patients who continued working during the lockdown. While investigators were unable to determine the exact reasons for glycemic control, but suggested it may have something to do with increased concern over disease management in the face of the pandemic.

"In addition, the knowledge that diabetes worsens the outcomes of COVID-19 may have improved patients' awareness and compliance to diabetes management,” wrote investigators.

Glycaemic Control Among People with Type 1 Diabetes During Lockdown for the SARS-CoV-2 Outbreak in Italy

,” was presented at EASD 2020 and published in 

Data from a group of type 1 diabetics from a diabetes center in Italy suggests time off work and in lockdown could have been helped some patients improve glycemic control.  

COVID-19 Lockdown May Have Improved Glycemic Control for Some Diabetics

New research from the University of Manchester offers an updated overview of the reduction in life expectancy associated with type 1 and type 2 diabetes compared against the general population.

European Association for the Study of Diabetes (EASD) 2020

 annual meeting, results of the study suggest the average person with type 1 diabetes will live nearly 8 years less and those with type 2 diabetes will live almost 2 years less than their counterparts in the general population.

"Knowledge of this may act as an incentive for clinicians to ensure that all people are on the best therapy to keep their blood sugar in the target range, and for those people to engage more strongly with their therapy and lifestyle recommendations,” noted study authors.

With many previous analyses of lost life years relying on older data, a team led by Adrian Heald, MD, sought to quantify the average reduction in life expectancy associated with type 1 and type diabetes, respectively, among patients using more recent data. With this in mind, investigators identified the UK National Diabetes Audit (NDA) and the Office for National Statistics (ONS) as data sources for their analysis.

Using the ONS, investigators performed a search of data from 2015-2017 and extracted actual mortality rates and projected life expectancy of the general population for each age year and sex. Through a search of the UK NDA from 2015-2016, investigators obtained information related to mortality rates for people with type 1 diabetes and type 2 diabetes in 5 different age groups and each sex as a ratio to the general population.

In total, investigators obtained data from more than 6000 general practices providing care to 41.3 million patients. Of these 41.3 million, 217k had type 1 diabetes and 2.5 million had type 2 diabetes.

Upon analysis, investigators found the average person with type 1 diabetes was 42.8 years of age and had a life expectancy from now of 32.6 years. In comparison, people the same age without diabetes were expected to live 40.2 years from now. For type 2 diabetes, the average patient was 65.4 years old and had a life expectancy from now of 18.6 years. In comparison, patients the same age without diabetes were expected to live 20.3 years from now.

Results of the investigators’ analysis also suggested each year with an HbA1c greater than 58 mmol/mol equated to a loss of around 100 life days for both type 1 and type 2 diabetes. Additionally, investigators noted their hope that further research into associations of glycemic control with mortality could improve care and management efforts.

“Linking poor glycemic control to expected mortality in such a quantitative way may incentivize clinicians and people with diabetes and poor blood sugar control to increase their efforts to achieve targets,” investigators added. Communication of life years lost from now to patients at the time of consultation with healthcare professionals and through messages publicized by advocacy groups such as Diabetes UK and other national/international patient facing organizations will be of great help in terms of dissemination of the conclusions of this study.”

Estimating life years lost to diabetes: outcomes from analysis of National Diabetes Audit and Office of National Statistics data

Cardiovascular Endocrinology and Metabolism.

Research presented at EASD 2020 provides an updated estimate of the life years lost as a result of type 1 and type 2 diabetes, respectively, among patients in the UK.

Study Estimates Average Life Years Lost from Type 1, Type 2 Diabetes

Results from a recent study of patients in a national registry is offering greater insight into the risk of falls and fall-related injuries in patients with 

The study, which examined risks associated with type 1 and type 2 diabetes separately, found patients with type 1 diabetes were at a 33% greater risk while patients with type 2 diabetes were at a 19% greater risk of falls than the general population.

"While of course we cannot do anything about getting older or our gender, diabetes—especially type 2 diabetes—use of medications and alcohol abuse could be potentially modifiable risk factors for falls,” concluded investigators. “Gaining further information on risk factors for falls could guide the management of diabetes treatment such as the choice of medication, which enables us to improve treatment particularly in people with a high risk of falls and fractures associated with high mortality."

Led by Nicklas Rasmussen, of the Steno Diabetes Center, the study was designed to tackle a pair of pressing questions through analysis of data within the Danish National Patient Register. The specific goals of the study were to estimate risk of falls and identify factors associated with increased falls and also to estimate differences in fall-related injuries and where they occur in those with type 1 and type 2 diabetes versus the general population. The study, which was presented at the 

 annual meeting, examined all data the within the registry from 1996-2017.

Through their search, investigators identified cohorts of 12,975 type 1 diabetics and 407,099 type 2 diabetes. From these populations, investigators created sex- and age-matched control groups from the general population. Of note, adjusted analyses performed in the study accounted for age, sex, diabetic complications, a history of alcohol abuse, and a history of medication.

Results of the investigators' query revealed the cumulative incidence rate of falls requiring hospitalization was 13.% among patients with type 1 diabetes and 11.9% in patients with type 2 diabetes. Upon analysis, results suggest type 1 diabetes was associate with a 33% greater risk of falls (HR, 1.33; 95% CI, 1.25-1.43) and type 2 diabetes Wass associated with a 19% greater risk of falls (HR, 1.19; 95% CI, 1.16-1.22).

The investigators' analysis also identified multiple other risk factors significantly associated with falls among patients in both groups. Among patients with type 1 diabetes, other risk factors included being female (T1: HR, 1.21; 95% CI, 1.13-1.29; T2: HR, 1.61; 95% CI, 1.58-1.64), older than 65 years of age (T1: HR, 1.52; 95% CI, 1.39-1.61; T2: HR, 1.32; 95% CI, 1.58-1.64), use not SSRI (HR, 1.35; 95% CI, 1.30-1.40; T2: HR, 1.32; 95% CI, 1.27-1.38), use of opioids (T1: HR, 1.15; 95% CI, 1.12-1.19; T2: HR, 1.09; 95% CI, 1.05-1.12), and a history of alcohol abuse (T1: HR, 1.77; 95% CI, 1.17-2.15; T2: HR, 1.88; 95% CI, 1.69-2.15).

Additionally, investigators found the incidence rate ratio(IRR) of fall-related injuries such as hip (IRR, 1.02; 95% CI, 1.01-1.04), radius (IRR, 1.39; 95% CI, 1.18-1.61), humerus (IRR, 1.24; 95% CI, 1.12-1.37), and skull/facial fractures (IRR, 1.15; 95% CI, 1.07-1.24) were greater among patients with type 2 diabetes. Among patients with type 1 diabetes, an increased IRR was only noted with hip fractures (IRR, 1.11; 95% CI, 1.11-1.23).

Increased risk of falls, fall-related injuries and fractures in people with type 1 and type 2 diabetes compared with the general population: a nationwide cohort study

A study from EASD 2020 found type 1 diabetes was associated with a 33% increase in risk of falls while type 2 diabetes was associated with a 19% increase in risk. 

Diabetics, Both Type 1 and Type 2, at Increased Risk of Falls, Fall-Related Injuries

 annual meeting suggests patients with rheumatoid arthritis were at a nearly 25% increased risk of developing diabetes compared to the general population.

The study, which was conducted by researchers from the University of Manchester, sheds further light on the potential impact of systemic inflammation associated with the common rheumatic disease.

"This finding supports the notion that inflammatory pathways are involved in the pathogenesis of diabetes,” said study investigators.

Led by Adrian Heald, MD, an honorary research fellow, the team of investigators from the University of Manchester sought to evaluate potential associations between inflammatory diseases and the onset of type 2 diabetes. With this in mind, they designed their study as a comprehensive search of the Medline, Embase, and Web of Science databases from inception through March 10, 2020.

Searching for studies comparing the risk of diabetes mellitus incidence in people with rheumatoid arthritis versus those in the general population, investigators identified a total of 3669 articles for potential inclusion in their analysis. After the application of inclusion criteria and abstracting screening, investigators identified 5 journal articles and 2 conference abstracts to be included in their final analysis.

From these studies, investigators obtained data related to 1,639,854 participants. Investigators noted most studies were population-based but 1 of the studies included was hospital-based. Additionally, investigators noted heterogeneity was observed in an I2 test (I2=96%; 

Upon analysis of these studies, investigators found rheumatoid arthritis was associated with a 23% increase in risk of diabetes mellitus incidence (pooled RR, 1.23; 95% CI, 1.07-1.40). In a sensitivity analysis, investigators found exclusion of the hospital-based study did not materially change the result (pooled RR, 1.23; 95% CI, 1.06-1.42).

“We suggest that more intensive screening and management of diabetes risk factors should be considered in people with rheumatoid arthritis. Agents that reduce systemic inflammatory marker levels may have a role in preventing type 2 diabetes. This may involve focusing on more than one pathway at a time,” investigators added.

The relation between rheumatoid arthritis and diabetes incidence: a systematic review and meta-analysis

A study from EASD 2020 suggests patients with RA could be at a nearly 25% increase in risk of developing type 2 diabetes later in life. 

Rheumatoid Arthritis Tied to 23% Increase in Risk of New Diabetes

New data released today from the Diabetes Prevention Program Outcomes Study (DPPOS) shows that in over 2000 patients followed for an average of 22 years, lifestyle programs and treatment with metformin continues to prevent the development of type 2 diabetes (T2D) in at risk populations.

New Data on Clinical Outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS)

were presented today at the American Diabetes Association’s® (ADA’s) 80th Virtual Scientific Sessions.

 a multicenter trial conducted from 1996 to 2001 that established the success of either an intensive lifestyle program or treatment with metformin to prevent or delay the development of T2D in individuals who were considered at high risk for developing the disease. The DPP demonstrated lifestyle intervention, aimed at achieving weight loss, and metformin treatment reduced the risk of T2D development by 58% and 31%, respectively, compared to placebo after an average of three years. Metformin, one of the most commonly used medications worldwide for the treatment of T2D, is currently not labeled by the FDA for prevention purposes, although it is approved in other countries.

88% of the original 3,234 DPP participants enrolled in the DPPOS, including the DPP participants who had developed T2D and those who still had not developed diabetes. Currently, after an average of 22 years of study, 75% of the participants who enrolled in the DPP who are still alive have continued to be evaluated. The mean age of the participants is now 72 years.

The newest results indicate that prevention effects in the original lifestyle group and metformin treatment group remain 22 years after the start of the study with a 25% and 18% reduced risk of diabetes development, respectively, compared with the original placebo group.

“The DPP/DPPOS is the longest duration and largest prevention study that continues to actively follow its participants,” said DPPOS chair David M. Nathan, MD, director of the Clinical Research Center and Diabetes Center at Massachusetts General Hospital and professor of medicine at Harvard Medical School. “The current results indicate that prevention of type 2 diabetes is possible and has important clinical benefits. The long-term benefits of the two DPP interventions on diabetes development, still present many years after they were started, are a testament to the power of these interventions and reinforce their importance in the reduction of diabetes.”

The participants who did not develop diabetes had a significant (57% and 37%) lower risk of developing early changes of eye and kidney disease, respectively, and a 39% lower risk of major cardiovascular disease endpoints, such as heart attacks and stroke.

There was no significant benefit in heart disease or the development of kidney disease or diabetic retinopathy with either of the individual interventions—metformin or the lifestyle intervention.However, stroke and cardiovascular events were reduced in the subgroup of people who started the study before age 45, and there was a non-significant (12%) lower risk of cancer in the Metformin group compared with the placebo group. The intensive lifestyle intervention group also had a long-term reduction in the development of frailty.

There was a modest increase in kidney disease with metformin, which appeared only in the oldest group of participants.

New data released today from the Diabetes Prevention Program Outcomes Study (DPPOS) shows that in over 2000 patients followed for an average of 22 years, lifestyle programs and treatment with metformin continues to prevent the development of type 2 diabetes in at risk populations.

Diabetes Study Shows Lifestyle Interventions and Metformin Continue to Prevent Type 2 Diabetes After 2 Decades

Environmental Determinants of Diabetes in the Young (TEDDY) study

 illuminate the environmental triggers that are thought to cause the autoimmune response leading to type 1 diabetes(T1D) and celiac disease. The data was presented in a symposium at the American Diabetes Association meeting.

TEDDY is an international multi-center trial researching the potential causes T1D in children. The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).It has been collecting prospective data since 2004, researching the link between genetic and environmental factors in the autoimmune destruction of the beta islet cells of the pancreas.

Although many children are genetically predisposed to T1D, not all children develop it, resulting in the conclusion that an environmental trigger is required. The study enrolls infants identified as “at-risk” for developing T1D and follows them for 15 years to look for the appearance of various beta-cell autoantibodies and diabetes. TEDDY has also studied biomarkers that can predict faster or slower progression to diabetes after the autoimmune destruction has begun.

An update of the results presented at the ADA meeting this week showed that the destruction of beta islet cells begins in the first two years of life, and that there are two clearly different genetic subtypes of T1D.

“There appear to be two subtypes of T1D that differ by genetic factors and immune phenotypes,” said study TEDDY co-chair Marian Rewers, MD, PhD, a professor of pediatrics and medicine and executive director of the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine. “Metabolomic biomarkers may offer clues to the subtypes and whether a child develops T1D. Interestingly, HbA1c has very different predictive characteristics for progression to clinical diabetes in children with islet autoantibodies, compared to adults with risk factors for type 1 diabetes.”

Research also showed that the persistent presence of enterovirus B species in a child’s stool predicts development of islet autoimmunity, especially the earlier subtype characterized by the presence of autoantibodies to insulin.

Researchers say there are also subtle differences in the composition and function of gut microbiome in children who develop islet autoantibodies, compared to controls, and data show that the early use of probiotics may decrease the risk, while use of antibiotics was not related to islet or celiac autoimmunity.

The study has also found potentially beneficial effects of vitamin D, vitamin C, or a diet rich in polyunsaturated fatty acids, though these observations need to be confirmed in randomized clinical trials.

Celiac disease shares many genetic factors with T1D, noted Dr. Rewers. For this reason, TEDDY investigators follow study participants for both T1D and celiac disease in an attempt to determine why some children with high-risk genes develop T1D or celiac disease, while most remain disease-free. Recently reported TEDDY 

showed an association between gluten consumption in the early years of childhood and an increased risk of celiac disease among genetically predisposed children.

“While T1D and celiac disease share a lot of genetic characteristics, there are intriguing differences in the ways these diseases develop and progress,” added Dr. Rewers. “TEDDY is contributing exciting clues for design of future trials to prevent both T1D and celiac disease.”

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Andrén Aronsson C, Lee HS, Hård Af Segerstad EM, et al. Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk. 

. 2019;322(6):514-523. doi:10.1001/jama.2019.10329

New data from the Environmental Determinants of Diabetes in the Young (TEDDY) study illuminate the environmental triggers that are thought to cause the autoimmune response leading to type 1 diabetes(T1D) and celiac disease. The data was presented in a symposium at the American Diabetes Association meeting.

Research Illuminates Origins of Type 1 Diabetes and Celiac Disease

Three highlights of obesity research examined the impact of corticosteroid use on prevalence of metabolic syndrome, explored the effects of a weight management program on job performance, and investigated the consequences of Vitamin D deficiency in overweight and obese children and adolescents.

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ENDO

Could corticosteroid use put your patients at a greater risk of metabolic syndrome?

Obesity Management: ENDO 2017 Highlights

Three studies from ENDO 2017 featured a noninvasive electromagnetic brain stimulation technique to help patients with obesity lose weight, a “smart” artificial pancreas system to improve blood glucose control, and a videoconferencing education system to improve care of complex diabetes cases in rural areas.

Three studies from ENDO 2017 focused on improving patient care through brain stimulation, an artificial pancreas system, and videoconferencing.

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