Effects on Insulin Resistance With Tadalafil in Type 2 Diabetes - a Double-blind, Placebo-controlled Crossover Study

Summary

The aim is to continue our program on PDE5 inhibition by evaluating effects on insulin resistance, including glucose metabolism and subclinical inflammation, after a 6-week administration of tadalafil in T2D patients. The primary objective is to study the effect of tadalafil compared with placebo on insulin sensitivity during a euglycemic hyperinsulinemic clamp. This is a double-blind, placebo-controlled crossover study with one study site. Twenty-five T2D patients will be recruited and randomized to per oral intake of tadalafil 20 mg o.d. for six weeks and after a wash-out period of eight weeks intake of placebo for another six weeks, or vice versa. At the end of each 6 week treatment period a glucose clamp, subcutaneous needle biopsies as well as muscle and subcutaneous microdialysis will be performed. Endothelial function tests and arginin stimulation of insulin secretion tests will be performed after 3 weeks in each treatment arm.

Timeline

Start

2015-11

Primary completion

2019-01

Completion

2019-01

Publications

• Fryk E, Rodrigues Silva VR, Strindberg L, Gisslen M, Zetterberg H, Blennow K, Jansson PA. Effect of 6-week tadalafil treatment on blood-based biomarkers of neurodegeneration: A post-hoc analysis of a randomized controlled trial. J Alzheimers Dis. 2026 Apr;110(3):1072-1078. doi: 10.1177/13872877261421227. Epub 2026 Mar 13.
• Fryk E, Rodrigues Silva VR, Bauza-Thorbrugge M, Schmelz M, Gan LM, Strindberg L, Jansson PA. Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial. EClinicalMedicine. 2023 May 4;59:101985. doi: 10.1016/j.eclinm.2023.101985. eCollection 2023 May.

Drugs

Indications