The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes.

Abstract

BACKGROUND:

There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity.

METHODS:

Patients with obesity (BMI, 35-50 kg/m2 ) were enrolled into a 12-week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two-part study, comprising a single-dose cross-over study (N = 12; 2.5 - 300 mg) and a 14-day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE24 ) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP-1, PYY3-36 , and GIP), insulin and glucagon.

RESULTS:

Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC0-4h ) and suppressed insulin by 90% (P < 0.01; incremental AUC0-4h ). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24-hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP-1 by 54% (P < 0.001) and PYY3-36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12-week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%-43% with licogliflozin vs 9%-11% with placebo in the 12-week study) were among the other gastrointestinal events reported.

CONCLUSION:

Licogliflozin treatment (1-84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.

• Authors: Yan-Ling He, William Haynes, Charles D Meyers, Ahmed Amer, Yiming Zhang, Ping Mahling, Anisha E Mendonza, Shenglin Ma, William Chutkow, Eric Bachman
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 21 Issue 6 Pg. 1311-1321 (06 2019) ISSN: 1463-1326 [Electronic] England
• PMID: 30724002 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• Anhydrides
• Blood Glucose
• Sodium-Glucose Transporter 2 Inhibitors
• Sorbitol
• licogliflozin

Topics

• Adult
• Anhydrides (administration & dosage, adverse effects, pharmacology)
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (blood, complications)
• Female
• Humans
• Male
• Middle Aged
• Obesity (blood, complications, drug therapy)
• Sodium-Glucose Transporter 2 Inhibitors (administration & dosage, adverse effects, pharmacology)
• Sorbitol (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• Young Adult