Noninsulin Therapies in Management of Type 1 Diabetes

With the increasing prevalence of double diabetes (features of type 2 diabetes in people with type 1 diabetes (T1D)), there is a growing interest in using noninsulin therapies to improve glycemic outcomes, promote weight loss, and reduce cardiovascular risk in T1D. In this narrative review, we summarize current literature and provide practical guidance for clinicians when considering these therapies.

Using a PubMed literature search, we identified 51 randomized clinical trials investigating sodium glucose co-transporter inhibitors (SGLTi:9), glucagon like peptide 1 receptor agonist (GLP1RA: 13), metformin (13), dipeptidyl peptidase-4 inhibitor (9), pramlintide (4), bromocriptine (1) and combination therapies (2) in T1D. Outcomes of interest included change in HbA1c, weight, total daily dose (TDD) of insulin, surrogate cardiovascular outcomes and safety parameters.

Data shows that GLP-1RAs and SGLTi have demonstrated the greatest efficacy in reducing HbA1c up to 0.7% and 0.5%, respectively, compared to placebo. GLP-1RAs reduced TDD of insulin by up to 18.5% and weight up to 9.3% (8.3 kg). SGLTi reduced insulin TDD by up to 15.3% and weight 5.3% (4.3 kg). Neither class increased the risk of severe hypoglycemia but SGLTi had a two-to-five-fold higher risk of diabetic ketoacidosis. Other agents (metformin, dipeptidyl peptidase-4 inhibitor and bromocriptine) failed to demonstrate a sustained glycemic efficacy in T1D.

GLP-1RA therapy has a great potential as adjunct therapy in T1D. SGLTi could be another beneficial therapy in T1D, however, more research is needed to improve diabetic ketoacidosis risk with this therapy. Efficacy trials of weekly GLP-1RA and its potential cardio-renal benefits in T1D are much needed.