Table 1.

Summary clinical studies in patients with diabesity treated with pramlintide. T1DM—type 1 diabetes mellitus; T2DM—type 2 diabetes mellitus; HbA1C—hemoglobin A1C.

Authors	Research Design (Primary Goal, Duration)	Number of Patients	Results	Main Conclusions
Karl D et al., 2007 [66]	Open-label study. Safety and efficacy of pramlintide therapy. Duration: 2 years.	166 insulin-treated patients with T2DM	The change in HBA1c from baseline was −0.56%. Pramlintide therapy notably reduced weight (−2.8 kg) and postprandial glucose excursions.	Pramlintide initiation and mealtime insulin reduction led to weight loss. It also improved postprandial glucose excursions and HBA1c.
Pencek R et al., 2010 [67]	Open-label, multicenter, observational study. Primary goal was to assess the risk of insulin-induced severe hypoglycemia after pramlintide initiation. Duration: 6 months	1297 patients with T1DM and T2DM with inadequate glycaemic control	After 3 months, the incidence of patient-ascertained severe hypoglycemia (PASH) was 2.8% in patients with T2DM and 4.8% in patients with T1DM.	The possibility of insulin-induced severe hypoglycemia after pramlintide therapy initiation is low in patients with T2DM or T1DM.
Riddle M et al., 2007 [68]	A randomized, double-blind, placebo-controlled, multicenter study. Safety of adding pramlinitide to insulin glargine therapy. Duration: one year.	212 patients with T2DM using insulin glargine in addition to pramlintide or placebo	Reductions in HBA1c (−0.70% against −0.36%) and postprandial glucose increase were more significant in pramlintide-treated patients. Pramlinitide-treated patients experienced weight loss (−1.6 kg), while placebo gained weight (+0.7 kg).	Pramlintide improved HBA1c and postprandial glucose with weight reduction in T2DM patients.
Peyrot M et al., 2010 [69]	A randomized, open-label, parallel-group, multicenter study. The effectiveness of basal insulin regimens with rapid-acting insulin or pramlintide. Duration: 9 months.	112 patients with T2DM and basal insulin therapy in addition to pramlintide or rapid-acting insulin	Total diabetes distress in pramlintide patients improved significantly. On the other hand, patients with rapid-acting insulin did not. The perception of hypoglycemia was improved only in pramlintide patients.	Adding pramlintide to basal insulin treatment improved life quality and satisfaction compared with rapid-acting insulin analogs.
Whitehouse et al., 2002 [70]	A double-blinded clinical trial with parallel assignment. Effects of pramlintide on HBA1c and weight. Duration: 52 weeks.	480 patients with T1DM	HBA1c was lower in patients with pramlintide (−0.39%) in comparison with placebo (−0.12%). The patients with pramlinitide had a weight loss (−0.5%) in contrast to placebo patients with weight gain (+1.0%).	Pramlintide has a positive effect on HBA1c and weight loss compared to placebo.
Ratner et al., 2000 [62]	The study was double-blinded with parallel assignment. Effects of pramlinitide on weight and HBA1c. Duration: 52 weeks.	538 patients with insulin-treated T2DM	The patients with pramlintide had a weight loss (−0.3% to −1.3% depending on the dosage); on the contrary, placebo patients had a weight gain (+1.0%). HBA1c was lower in patients with pramlintide (−0.3% to −6.0% depending on the dosage) in comparison with placebo (−0.2%).	Pramlintide has a positive effect on weight loss and HBA1c compared with placebo.
Hollander et al., 2003 [63]	The study was double-blinded with parallel assignment. Pramlintide effects on HBA1c and weight. Duration: 52 weeks.	498 patients with T2DM	HBA1c was lower in patients with pramlinitide (−0.35% to −0.62% depending on the dosage) than a placebo (−0.22%). The patients with pramlintide had a weight loss (−0.5% to −1.2% depending on the dosage); on the contrary, placebo patients had a weight gain (+0.7%).	Pramlintide has a positive effect on HBA1c and weight loss compared to placebo.
Gottlieb et al., 1999 [71]	The study was double-blinded with parallel assignment. Effects of pramlintide on HBA1c and weight. Duration: 26 weeks.	499 patients with T2DM	The patients with pramlintide had a weight loss (−0.8% to −1.4% depending on the dosage); on the contrary, placebo patients had a weight gain (+0.1%). HBA1c was lower in patients with pramlinitide (−0.3% to −0.4% depending on the dosage) in comparison with placebo (−0.1%).	Pramlintide has a positive effect on HBA1c and weight loss compared to the placebo.