Epidemiological data indicate that people with type 1 diabetes experience cardiovascular events on average more than a decade earlier and have lifespans roughly 13 years shorter than the general population. Similarly, the risk of incident heart failure is alarmingly high in people with type 1 diabetes. For example, recent epidemiological studies have cited a relative risk that ranges anywhere from 2.68 to 4.32 when compared to age-matched controls without diabetes.
The importance of optimal glycemic control in preventing chronic macrovascular complications in people with type 1 diabetes is well-established and was first demonstrated in the Diabetes Control and Complications Trial. However, recent real-world observational analyses have shown that many (ranging anywhere from 42.3-79%) people with type 1 diabetes do not achieve recommended glycemic targets and that age-adjusted cardiovascular disease mortality rates remain nearly threefold higher than the general population even when target hemoglobin A1c (HbA1c) levels <7% are achieved. Beyond glucose, recent improvements in mean blood pressure and lipids have also reduced rates of cardiovascular complications in this population overall. The difference in cardiovascular risk between people with type 1 diabetes and the general population endures despite these improvements.
A growing number of medications that offer glycemic as well as cardiorenal benefits are now FDA-approved for people with type 2 diabetes; however, none of these medications currently carry an FDA indication for use in people with type 1 diabetes. Thus, there is an urgent need to identify adjunct medicines that can be paired with insulin to optimize gluco- and cardiometabolic health in this population. This topic was well-addressed in numerous presentations at the recent 85th Scientific Sessions of the American Diabetes Association in Chicago. First on this list was a symposium entitled “Adjunctive Therapies to Prevent Complications in Type 1 Diabetes,” wherein several potential adjunct therapies (i.e., glucagon receptor antagonists, glucokinase activators, sodium-glucose transporter inhibitors, and incretins) were discussed. The pathophysiologic basis for their potential benefit was presented along with results from early clinical trials. Later the same day, a second session presented results from the highly-anticipated ADJUnct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D) Trial. In this 26-week, double-blind trial, 72 adults with type 1 diabetes using an automated insulin delivery (AID) system and with a body mass index ≥30 kg/m2 were randomized in a 1:1 ratio to receive once-weekly semaglutide (with dose escalation up to 1 mg, if needed) or placebo. The trial utilized a primary composite endpoint that consisted of achieving all of the following elements: continuous glucose monitoring (CGM)–based time-in-range (i.e., 70-180 mg/dL) of >70%; time-below-range (i.e., <70 mg/dL) of <4%; and weight reduction of ≥5%. Excitingly, a significantly greater percentage of participants in the semaglutide group than in the placebo group achieved the primary composite outcome (36% vs. 0%; P<0.001) with improvements in hemoglobin A1c, CGM time-in-range, body weight, and total daily insulin dose (16). These results are very exciting given the cardiorenal benefits observed with studies of semaglutide in people with type 2 diabetes.
This year’s ADA Scientific Sessions highlighted exciting results from several medication classes that may serve as ideal adjunct therapies to insulin in people with type 1 diabetes. As these investigations continue, it is increasingly likely that we will soon be able to offer adjunct therapies that improve glycemic control and provide cardiorenal benefits to those living with this disease.
Dr. Horton has no conflicts of interest to report.
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