A new meta-analysis combining 22 studies, to be presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany (2-6 October), shows that tirzepatide is superior to semaglutide for both control of blood sugar and in terms of amount of body weight lost by patients. The study is by Dr Thomas Karagiannis, Aristotle University of Thessaloniki, Thessaloniki, Greece, and colleagues.

Semaglutide is approved for treatment of type 2 diabetes and also obesity/weight loss management. Tirzepatide has been approved for treating type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management. There are few randomised controlled trials (RCTs) directly comparing subcutaneous tirzepatide with subcutaneous semaglutide*. In this new research, the authors combined the data from 22 available trials to perform a meta-analysis to compare tirzepatide with semaglutide in terms of their efficacy and safety in people with type 2 diabetes.

The authors searched Medline and the Cochrane Library for RCTs that assessed a maintenance dose of subcutaneous tirzepatide 5, 10, or 15 mg once-weekly or subcutaneous semaglutide 0.5, 1.0, or 2.0 mg once-weekly for at least 12 weeks. Comparators were any of the eligible doses of tirzepatide and semaglutide, placebo, and also other glucose-lowering drugs provided they were directly compared to tirzepatide and semaglutide in at least one trial. The meta-analysis then calculated any differences in effects on HbA1c (glycated haemoglobin, a measure of blood sugar control), body weight, and also the risk of adverse events.

The 22 RCTs included data from 18,472 patients, all with a diagnosis of type 2 diabetes. The authors found that tirzepatide 15 mg was the most efficacious in reducing HbA1c versus placebo (mean difference -2.00%), followed by tirzepatide 10 mg (-1.86%) and semaglutide 2.0 mg (-1.62%). Each of the three tirzepatide doses reduced HbA1c more than the respective low-, medium-, and high-dose of semaglutide. Versus placebo, tirzepatide was more efficacious in reducing body weight (-10.96 Kg, -8.75 Kg, and -6.16 Kg for tirzepatide 15, 10, and 5 mg respectively) than semaglutide (-5.24 Kg, -4.44 Kg, and -2.72 Kg for semaglutide 2.0, 1.0, and 0.5 mg respectively) (Figure in full abstract, link below). Regarding between-drug comparisons, both tirzepatide 10 and 15 mg were more efficacious in lowering body weight versus semaglutide 0.5, 1.0, and 2.0 mg, while tirzepatide 5 mg was more efficacious versus semaglutide 0.5 and 1.0 mg.

Although not in the linked abstract below, the authors have been able to provide results for change in body weight from the analyses comparing tirzepatide and semaglutide (rather than versus placebo as shown in the figure in the abstract). These numerical values will be presented in the oral presentation in the congress.

The actual differences in change in body weight (mean difference) for the following comparisons are (using data from the above paragraph and abstract figure):

• Tirzepatide 15 mg versus semaglutide 2.0 mg = -5.72 Kg (ie, a mean of 5.72kg more weight lost in those taking tirzepatide 15 mg versus those taking semaglutide 2.0 mg)
• Tirzepatide 10 mg versus semaglutide 2.0 mg = -3.52 Kg
• Tirzepatide 5mg versus semaglutide 1.0 mg = -1.72 Kg

The authors explain: “In summary the three tirzepaide doses were more effective than the 3 respective semaglutide doses, with the difference between the two drugs being larger with the higher doses.”

As compared to placebo, all doses of tirzepatide and semaglutide increased risk for gastrointestinal adverse events, with tirzepatide 15 mg yielding the highest increased risk (3.6 times) for nausea, vomiting (4.4 times) and diarrhea (double the risk). Between-drug comparisons yielded non-statistically significant results, except for tirzepatide 15 mg versus semaglutide 1.0 mg (39% increased vomiting risk) and 0.5 mg (85% increased vomiting risk), and tirzepatide 15 mg versus semaglutide 0.5 mg (45% increased risk of nausea). There was no difference between tirzepatide, semaglutide and placebo regarding risk for serious adverse events.
 

The authors conclude: “In people with type 2 diabetes, tirzepatide 5, 10, and 15 mg were more efficacious in reducing HbA1c compared to semaglutide 0.5, 1.0, and 2.0 mg, respectively. Tirzepatide also was also more effective for weight loss than semaglutide, with a larger weight-loss effect at higher doses. High-dose tirzepatide (15 mg) was associated with increased risk for vomiting versus low- and medium-dose semaglutide.”

*Note to editors: Of the 22 trials included in the meta-analysis, there are 2 RCTs comparing tirzepatide with semaglutide (SURPASS-2 and another smaller trial). Both trials were included in the meta-analysis. The 20 remaining rials compared either semaglutide or tirzepatide with a common comparator (placebo or basal insulin or other GLP-RA-1 drugs) and were used to produce indirect comparisons between tirzepatide and semaglutide.

This press release is based on an early release of oral presentation 5 at the European Association for the Study of Diabetes (EASD) Annual Meeting in Hamburg, 2-6 October. All accepted abstracts have been extensively peer reviewed by the congress selection committee. There is no full paper at this stage, but the authors are happy to answer your questions. The research has not been submitted to a medical journal for publication. As it is an oral presentation there is no poster available.

New research to be presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany (2-6 October) shows that, following a heart attack, there have been falls in the death rates of both people without diabetes and those with type 2 diabetes, but not those with type 1 diabetes. The study is by Dr Linn Glynn, Karolinska Institutet, Stockholm, Sweden, and colleagues.

Earlier studies have demonstrated that people with diabetes have a worse outcome after heart attacks (myocardial infarction [MI]), compared to people without diabetes. In contrast, recent studies have shown a substantially decline in overall mortality and cardiovascular (CV) outcome among people with diabetes. However, trends in survival after a first heart attack in people with diabetes and without diabetes have still not been extensively studied.

The authors identified, using data from between 2006 to 2020, 2,527 individuals with type 1 diabetes (T1D), 48,321 individuals with type 2 diabetes (T2D) and 243,170 individuals without diabetes with a first heart attack in national healthcare registries. The outcomes measured were trends in survival, (overall mortality and cardiovascular [CV] death), and major cardiovascular events (MACE), meaning the combined outcomes of non-fatal stroke, non-fatal MI, CV death and hospitalised heart failure. Computer and statistical modelling was used to establish any variations in these outcomes.

Individuals with T1D were younger (62 years,) and more often women (44%) compared to individuals with T2D (75 years,) women (38%), and to the control group without diabetes (73 years) women (38%). Three-year trends in death, CV death and MACE between groups are shown in the full abstract.

During follow-up and after multiple adjustments (sex, age, comorbidities, socioeconomic factors and medication) there was a significant decreased annual incidence trend for all cause death in control group (-1.9% per year) and individuals with T2D (-1.3% per year) with no such trend in individuals with T1D (no change). Corresponding numbers for CV death were for control group -2.0% per year, T2D -1.6% year, and T1D -0.5% per year, but the result for T1D was not statistically significant. For MACE, incidence in the control group fell by 2.3% per year, T2D by 1.9% per year and T1D by 0.6% per year, but again the result for T1D was not statistically significant.

Discussing potential reasons for the findings, the authors say that the standard care following a heart attack has improved with more availability of, for example percutaneous coronary intervention and better overall medical treatment. However, this standard of care should have improved in all three groups.

In this study population, the authors say that people with T1D had a longer duration of diabetes and a higher mean glycated haemoglobin (a measure of the average blood sugar level over the past 3 months) than people with T2D, which might have an impact on the risk of developing a heart attack as well as the prognosis following a heart attack.

The authors conclude: “During the last 15 years, the risk of death and major cardiovascular events in people without diabetes and with type 2 diabetes after having a first-time heart attack has decreased significantly. In contrast, this decreasing trend was absent in people with type 1 diabetes.  Our study highlights the urgent need for understanding the cardiovascular risk in people with T1D.”

Racial and ethnic inequities in diabetes have been established following gestational diabetes, but these inequities are substantial and have been an overlooked facet of maternal health equity, according to a new study by epidemiologist Teresa Janevic, PhD, associate professor of Epidemiology at Columbia University Mailman School of Public Health. Until now there was limited research on racial and ethnic disparities in type 2 diabetes after gestational diabetes mellitus (GDM). The findings are published online in the journal Obstetrics & Gynecology.

“Very few studies have examined prenatal, social, or structural determinants of type 2 diabetes after GDM,” said Janevic. “Our study has several strengths. It is the largest cohort study to date on racial and ethnic disparities after GDM, allowing us to explore potential pathways to these disparities.”

Gestational diabetes mellitus is diagnosed in about 8 percent of pregnant people in the U. S. and especially affects underserved communities of color..

The researchers used both the birth and hospital records to define the GDM cohort and to establish covariates, an approach with high validity.

Using 2009–2011 New York City birth and hospital data and 2009–2017 New York City A1c Registry data, the researchers classified type 2 diabetes as two hemoglobin A1c test results of 6.5 percent or higher. They also estimated associations between race and ethnicity and 8-year type 2 diabetes incidence, with data modeling techniques.

The results showed a fourfold increased risk of type 2 diabetes after gestational diabetes mellitus among Black individuals and a threefold increased risk among Hispanic and South and Southeast Asian individuals relative to White individuals.

The data included 22,338 patients with gestational diabetes.  The 8-year type 2 diabetes incidence was 12 percent overall and 18.5 percent in Black, 17 percent in South and Southeast Asian, 15 percent in Hispanic, and 5.5 percent in East and Central Asian patients, compared to 5 percent in White individuals.

Of individuals identified with GDM, 78 percent had an Hb A1c test during the follow-up period. Among Black and Hispanic individuals, the percent was 82 percent, among Asian individuals, 78 percent, and among White individuals, 68 percent.

Social, structural, and clinical characteristics at the time of delivery explain 46 percent of the increased risk of postpartum diabetes among Hispanic people, 27 percent among Black people and 14 percent of the increased risk among South/Southeast Asian people, thus creating an opportunity to intervene on life-long cardio-metabolic inequities.

Routinely measured social determinants of health at the time of delivery such as education and insurance status had weaker associations with later diabetes in South Asian, Black, and Hispanic pregnant people than in non-Hispanic White pregnant people, showing the need to learn how structural racism influences postpartum cardiometabolic risk in these groups, according to Janevic and colleagues.

“While racial and ethnic inequities are substantial in type 2 diabetes after GDM, the weak associations we see of common social or structural measures and BMI in Black, Hispanic and South and Southeast Asian individuals demonstrate the need for greater understanding of how structural racism influences postpartum cardiometabolic risk in these groups,” observed Janevic.

Within 8 years after experiencing gestational diabetes in pregnancy, an estimated 1 in 5 Black patients, 1 in 6 South or South Asian patients, 1 in 7 Hispanic patients, and 1 in 20 non-Hispanic White patients will have type 2 diabetes.

Health care during pregnancy is a rare point of care with the health system for many people and, therefore, serves as an opportunity to intervene early to reduce life-course differences in type 2 diabetes, Janevic points out.

“Our findings underscore the opportunity for GDM as an intervention point for life-course type 2 diabetes inequities and stress the importance of racial and ethnic disparities in GDM outcomes beyond the current pregnancy,” said Janevic. “We call for further work using multiple approaches – policy-level changes, along with clinical interventions targeting individuals, — to counter structural racism and to eliminate disparities.”

Paresh Dandona, MD, PhD, is the lead author on the study. CREDIT Sandy Kicman/University at Buffalo

Treating newly diagnosed Type 1 diabetes patients with semaglutide (trade names Ozempic, Wegovy and Rybelsus) may drastically reduce or even eliminate their need for injected insulin.

Those are the remarkable findings of a small University at Buffalo study reported in the New England Journal of Medicine and published online on Sept. 6.

“Our findings from this admittedly small study are, nevertheless, so promising for newly diagnosed Type 1 diabetes patients that we are now absolutely focused on pursuing a larger study for a longer period of time,” says Paresh Dandona, MD, PhD, SUNY Distinguished Professor in the Department of Medicine, former chief of the Division of Endocrinology in the Jacobs School of Medicine and Biomedical Sciences at UB and senior author on the paper.

A total of 10 patients at UB’s Clinical Research Center in the Division of Endocrinology were studied from 2020 to 2022, all of whom had been diagnosed in the past three to six months with Type 1 diabetes. The mean HbA1c level (an individual’s average blood sugar level over 90 days) at diagnosis was 11.7, far above the American Diabetes Association’s HbA1c recommendation of 7 or below.

The patients were treated first with a low dose of semaglutide while also taking meal-time (bolus) insulin and basal (background) insulin. As the study continued, semaglutide dosing was increased while mealtime insulin was reduced in order to avoid hypoglycemia.

“Within three months, we were able to eliminate all of the mealtime insulin doses for all of the patients,” says Dandona, “and within six months we were able to eliminate basal insulin in 7 of the 10 patients. This was maintained until the end of the 12-month follow-up period.”

During that time, the patients’ mean HbA1c fell to 5.9 at six months and 5.7 at 12 months.

Applying Type 2 diabetes drugs to treat Type 1 diabetes

For more than a decade, Dandona has been interested in how drugs developed for Type 2 diabetes might be utilized in treating Type 1 diabetes as well.

He and his colleagues were the first to study how liraglutide, another drug for Type 2 diabetes, might work in patients with Type 1 diabetes in a study he published in 2011.

“As we extended this work, we found that a significant proportion of such diabetics still have some insulin reserve in the beta cells of their pancreas,” Dandona explains. “This reserve is most impressive at the time of diagnosis, when 50% of the capacity is still present. This allowed us to hypothesize that semaglutide, which works through stimulation of insulin secretion from the beta cell, could potentially replace mealtime insulin administration.”

From the outset, the goal of the current study was to see if semaglutide treatment could be used to replace mealtime insulin, thereby reducing the insulin dosage, improving glycemic control, reducing the HbA1c and eliminating potentially dangerous swings in blood sugar and hypoglycemia.

The most common side effects for patients were nausea and vomiting as well as appetite suppression, which led a number of patients to experience weight loss, an outcome that Dandona says is generally an advantage since 50% of patients with Type 1 diabetes in the U.S. are overweight or obese.

“As we proceeded with the study, we found that even the dose of basal insulin could be reduced or eliminated altogether in a majority of these patients,” he says. “We were definitely surprised by our findings and also quite excited. If these findings are borne out in larger studies over extended follow-up periods, it could possibly be the most dramatic change in treating Type 1 diabetes since the discovery of insulin in 1921.”

Advancements that could lead to earlier diagnosis and treatment for diabetic retinopathy, a common complication that affects the eyes, have been identified by a multi-department research team from Michigan State and other universities.

Their findings were recently published in Diabetologia, the official journal of the European Association for the Study of Diabetes. Additional contributors are from the University of Alabama at Birmingham, Case Western Reserve University and Western University of Health Sciences. The study was funded by the National Eye Institute.

Researchers found that diabetes, age-related health conditions and other metabolic disorders can lead to a buildup of cholesterol in the retina. This tends to crystalize and contribute to the development of diabetic retinopathy.

Crystalized deposits are very reflective and can be seen in images of the retina. This is important because noninvasive retina evaluations can be done by most optometrists, creating an opportunity for earlier diagnosis for more people. 

“Retinopathy is the leading cause of preventable blindness and one of the most feared complications of Type 1 and Type 2 diabetes,” explained Julia Busik, MSU professor emeritus of physiology. “Within 20 years of developing diabetes, every individual with either Type 1 or Type 2 diabetes will have some degree of retinopathy. Current treatment approaches are very invasive and are only directed at the very late stage of retinopathy.”

“We are actively pursuing what can be done to lower cholesterol in the retina,” said Tim Dorweiler, a doctoral candidate in the Molecular, Cellular and Integrated Physiology Program at MSU and first author of the paper. “The retina is a very isolated organ, just like the brain, and both have a blood barrier that separates them from the rest of the body. This is what makes the retina hard to study and extremely complex.”

George Abela, chief of the MSU Division of Cardiology, said that these cholesterol crystals are like the crystals found in atherosclerotic plaque that can form in arteries and cause heart attacks, a finding discovered in his lab at MSU. He helped the research team identify ways to scan retinas using modified tissue preparation for scanning electron microscopy. This also helps researchers analyze the composition of the crystals, which typically result when there is too much cholesterol in one place.

There is also hope that new treatments to address crystals formed by cholesterol could be less invasive than current options for diabetic retinopathy. And there are questions about other areas of the body where these crystals could be treated to prevent other diseases.