Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

Background: In Type 1 diabetes (T1D), according to the most recent guidelines, the everyday glucose-lowering treatment is still restricted to the use of subcutaneous insulin, while multiple therapeutic options exist for Type 2 diabetes (T2D). Methods: For this narrative review we unsystematically screened PubMed and Embase to identify clinical trials which investigated glucose-lowering agents as an adjunct to insulin treatment in people with T1D. Published studies up to March 2022 were included. We discuss the safety and efficacy in modifying cardiovascular risk factors for each drug, the current status of research, and provide a clinical perspective. Results: For several adjunct agents, in T1D, the scientific evidence demonstrates improvements in HbA1c, reductions in the risk of hypoglycemia, and achievements of lower insulin requirements, as well as positive effects on cardiovascular risk factors, such as blood lipids, blood pressure, and weight. As the prevalence of obesity, the major driver for double diabetes, is rising, weight and cardiovascular risk factor management is becoming increasingly important in people with T1D. Conclusions: Adjunct glucose-lowering agents, intended to be used in T2D, bear the potential to beneficially impact on cardiovascular risk factors when investigated in the T1D population and are suggested to be more extensively considered as potentially disease-modifying drugs in the future and should be investigated for hard cardiovascular endpoints.