Pramlintide, an amylin analog, is an agent that delays gastric emptying, blunts pancreatic secretion of glucagon, and enhances satiety. It is an FDA-approved therapy for use in type 1 diabetic patients and has been shown to reduce A1C, induce weight loss, and lower insulin dose. However, it is only indicated for adults. Two 52-week trials of pramlintide (n = 1,131; age >18 years) showed A1C reductions of ~0.3–0.4%.[77,78] In both studies, a greater proportion of participants achieved an A1C target of <7% with the therapy than without the therapy. There are a few small, short-term studies of pramlintide use in children with type 1 diabetes, with outcomes similar to those in the adult studies. Clearly, larger, long-term studies are needed in pediatrics.
Injectable glucagon-like peptide-1 (GLP-1) agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors are increasingly being studied in the type 1 diabetic population, but are not approved by the FDA for this indication. GLP-1 agonists delay gastric emptying, suppress the postprandial rise in glucagon secretion, and may increase satiety. Preliminary studies indicate that these agents may also facilitate weight loss. Further long-term clinical trials in type 1 diabetic patients are needed.
Sodium-glucose Cotransporter 2 Inhibitors
Sodium-glucose cotransporter 2 (SGLT2) inhibitors work by inhibiting glucose reabsorption in the kidney and are also being tested in individuals with type 1 diabetes. These agents provide insulin-independent glucose lowering by blocking glucose reabsorption in the proximal renal tubule, leading to weight loss and A1C reduction in individuals with type 2 diabetes. However, insufficient data exist to recommend clinical use of these agents in type 1 diabetes at this time.
Metformin is a biguanide that decreases hepatic gluconeogenesis and is used as first-line therapy in type 2 diabetes. It has been shown to have some benefit in reducing insulin doses and weight in small studies in patients with type 1 diabetes and is now being evaluated more fully for use in patients with type 1 diabetes. Two randomized controlled trials are currently under way evaluating metformin in type 1 diabetic patients. The first study is in adults and is using carotid intima-medial thickness as an outcome measure (ClinicalTrials.gov identifier: NCT01483560). The second study is focusing on overweight or obese youths between the ages of 12 and 19 years who require ≥0.85 units/kg/day of insulin (ClinicalTrials.gov identifier: NCT01808690). Results are currently pending.
Pramlintide may be considered for use as adjunctive therapy to prandial insulin in adults with type 1 diabetes failing to achieve glycemic goals. (B)
Evidence suggests that adding metformin to insulin therapy may reduce insulin requirements and improve metabolic control in overweight/obese patients and poorly controlled adolescents with type 1 diabetes, but evidence from larger longitudinal studies is required. (C)
Current type 2 diabetes medications (GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors) may be potential therapies for type 1 diabetic patients, but require large clinical trials before use in type 1 diabetic patients. (E)
Diabetes Care. 2014;37(7):2034-2054. © 2014 American Diabetes Association, Inc.