Hormonal
GIP-GLP-1 co-agonists (e.g., tirzepatide) produce superior weight loss and glycemic control compared to GLP-1 receptor agonists alone in patients with type 2 diabetes and obesity.
For patients with T2DM and obesity, combining GIP and GLP-1 activity in a single weekly injection (like tirzepatide) is more effective for weight loss and blood sugar control than using GLP-1 agonists alone. This works despite GIP being ineffective on its own in diabetic patients, likely due to altered receptor signaling in the combined molecule.
A 6 months treatment with this compound resulted in near-normalization of glycated hemoglobin levels and weight losses reaching two-digit percentages, with both effects exceeding what was obtained in the same study with a long-acting GLP-1 receptor agonist, dulaglutide.
Why this rating
Based on cited Phase 2 clinical trial data (Frias et al.) comparing active treatments.
Source
GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists
Jens J. Holst et al. · The Journal of Clinical Endocrinology & Metabolism · 2020
DOI 10.1210/clinem/dgaa327
More from this paper
- GIP receptor antagonists can promote weight loss in non-human primates and rodents, challenging the view that GIP promotes obesity.Moderate
- The efficacy of GIP-GLP-1 co-agonists may be explained by biased agonism and altered receptor internalization, which prevents the desensitization seen with pure GIP agonists.Moderate
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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