T1DM Through the Life Span: ADA Position Statement
T1DM Through the Life Span: ADA Position Statement
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%. 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 (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.
Recommendations.
Adjunctive Therapies
Pramlintide
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%. 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.
Incretin-based Therapies
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
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.
Recommendations.
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)
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