Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis

Abstract

AimsWe aim to assess the efficacy and safety of pramlintide plus insulin therapy in patients with type 1 diabetes.MethodsWe included clinical studies comparing pramlintide plus insulin to placebo plus insulin. Efficacy was reflected by glycemic control and reduction in body weight and insulin use. Safety concerns were hypoglycemia and other adverse events. Subgroup analysis was performed for different doses (30, 60, 90 µg/meal) and durations (≤4, 26, 29, >29 weeks) of the treatment.ResultsA total of 10 randomized placebo-controlled studies were included for this meta-analysis (pramlintide, n=1978; placebo, n=1319). Compared with controls, patients given pramlintide had significantly lower HbA1c (p < 0.001), total daily insulin dose (p = 0.024), mean mealtime insulin dose (p < 0.001), body weight (p < 0.001) and postprandial glucose level (p = 0.002). The addition of pramlintide increased the incidence of nausea (p < 0.001), vomiting (p < 0.001), anorexia (p < 0.001) and hypoglycemia (p < 0.05) at the initiation of the treatment. The efficacy and adverse reactions of pramlintide were largely significant for the different doses and durations of the treatment.ConclusionsThe addition of pramlintide to insulin therapy in patients with type 1 diabetes improves glycemic control and reduces insulin requirement and body weight while bringing transient hypoglycemia and digestive disorders.

The changing face of paediatric diabetes

“…Pramlintide is a synthetic analogue of amylin, which is co-secreted with insulin postprandially to inhibit glucagon release, slow gastric emptying and signal satiety and is deficient in type 1 diabetes. In adults with type 1 diabetes, pramlintide resulted in a decrease in postprandial hyperglycaemia and glucagon, HbA 1c and weight compared with insulin-only therapy [80,81]. Other agents being investigated in type 1 diabetes are thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, drugs used in type 2 diabetes [82,83].…”

Non‐insulin treatments for Type 1 diabetes: critical appraisal of the available evidence and insight into future directions

“…The efficacy and adverse reactions of pramlintide were largely significantly differed according to dose and duration of treatment [15]. Pramlintide increased the incidence of nausea, vomiting, anorexia and hypoglycaemia at the initiation of treatment.…”

“…Pramlintide increased the incidence of nausea, vomiting, anorexia and hypoglycaemia at the initiation of treatment. The efficacy and adverse reactions of pramlintide were largely significantly differed according to dose and duration of treatment [15]. These adverse events were mostly of mild to moderate intensity, occurred early in the course of treatment and, with continuation of therapy,…”

Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4‐week, double‐blind, randomized, placebo‐controlled phase 2 trial

“…Several antihyperglycaemic agents (ie, pramlintide, metformin and liraglutide) with low risk of hypoglycaemia and weight gain in participants with type 2 diabetes mellitus (T2DM) improve glycaemic control and/or decrease insulin dose and body weight as adjuncts to insulin therapy in participants with T1DM . However, these medications have limitations in T1DM, such as increased risk of undesirable effects (ie, nausea, vomiting, anorexia and hypoglycemia), absence of sustained effect on glycaemic control, and increased rates of symptomatic hypoglycaemia, hyperglycaemic episodes with ketosis and diabetic ketoacidosis (DKA) when compared with placebo . Therefore, an adjunct to insulin treatment with a more favourable benefit/risk profile would be highly desirable in patients with T1DM.…”