ZP7570
Evidence Grade E — Very limited evidence. 3 published studies. 2 registered clinical trials.
Dapiglutide is a first-in-class molecule from Zealand Pharma that uniquely combines GLP-1 activity (appetite suppression) with GLP-2 activity (intestinal repair and anti-inflammatory effects). No other drug in development achieves this dual mechanism. Originally developed for short bowel syndrome, its development focus has shifted toward obesity and metabolic disease.
3 published studies: 1 human, 1 animal, 0 in-vitro, 0 reviews
Dapiglutide is in early clinical development (not yet approved). Phase Ib results showed up to 11.6% weight loss at 28 weeks. A Phase IIa study showed more modest results (4.3% at 12 weeks), considered disappointing relative to expectations. Good tolerability has been demonstrated across trials.
Dapiglutide's unique dual GLP-1/GLP-2 mechanism is scientifically novel, but early clinical results have been mixed. The GLP-2 intestinal repair component provides a differentiated mechanism, but whether it translates to clinical advantages over GLP-1-only or GLP-1/glucagon approaches remains to be demonstrated.
Dapiglutide simultaneously activates two complementary intestinal receptors: GLP-1R (appetite suppression, weight loss) and GLP-2R (intestinal growth, gut barrier strengthening, anti-inflammatory effects). The GLP-2 component may address gut barrier dysfunction and intestinal inflammation that are increasingly recognised as contributors to metabolic disease.
Early clinical results have been mixed. A Phase Ib study showed up to 11.6% weight loss at 28 weeks, but a Phase IIa study with a lower dose produced a more modest 4.3% at 12 weeks, considered disappointing relative to expectations. Sample sizes have been small (30-54 patients). The dual GLP-1/GLP-2 mechanism is scientifically novel — the GLP-2 component could address gut barrier dysfunction and intestinal inflammation increasingly recognised as contributors to metabolic disease — but whether this translates to clinical advantages over simpler approaches remains unproven. Phase IIb results are needed to determine the compound's viability in the competitive obesity space.
A Trial Comparing Pharmacokinetics, Safety and Tolerability of Two Subcutaneous Concentrations of Dapiglutide
Dapiglutide for the Treatment of Obesity
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Exenatide was the first GLP-1 receptor agonist approved anywhere, reaching the market as Byetta in April 2005. The once-weekly formulation Bydureon followed in 2012. Clinical trials showed blood sugar reductions (HbA1c) of 1.6–1.9% and modest weight loss of 2–4 kg. The EXSCEL cardiovascular outcomes trial, involving over 14,700 patients, showed a trend toward cardiovascular benefit but narrowly missed statistical significance. While exenatide was groundbreaking as the first in its class, it has been largely overtaken by newer GLP-1 treatments that offer greater efficacy, less frequent dosing, and proven cardiovascular benefits. It remains available and in clinical use, particularly in combination products.
Lixisenatide was marketed as Adlyxin in the US (approved July 2016), though it has since been discontinued in the US market. The ELIXA cardiovascular trial, involving over 6,000 patients, was the first cardiovascular outcomes trial for any GLP-1 medication to report results. It showed a neutral cardiovascular profile — neither harmful nor beneficial — meeting safety requirements but not demonstrating the heart benefits later shown by semaglutide and liraglutide. Lixisenatide found its primary clinical role in combination with basal insulin, marketed as Soliqua (lixisenatide plus insulin glargine). This combination addresses both fasting blood sugar (via insulin) and post-meal spikes (via lixisenatide) in a single daily injection. As a standalone treatment, it has been largely superseded by more potent GLP-1 medications.
Pramlintide is marketed as Symlin (approved March 2005) and remains the only approved amylin-based treatment. It is used alongside mealtime insulin in both type 1 and type 2 diabetes. Clinical trials showed modest blood sugar improvements (HbA1c reductions of 0.2–0.6%) and approximately 2.3 kg of weight loss — less dramatic than GLP-1 treatments but meaningful as an add-on therapy. Symlin carries a boxed warning for severe hypoglycaemia, particularly when combined with insulin, and requires careful dose adjustment. Practical uptake has been limited by the need for separate injections at each meal alongside existing insulin injections. Despite its modest clinical impact, pramlintide remains the only medication that addresses the amylin deficiency in diabetes, filling a distinct biological role that GLP-1 treatments do not cover.
