Quitting Smoking With Varenicline Didn't Cause Weight Gain in Diabetic Patients and Raised GLP-1 Levels | Research

The takeaway

Diabetic and prediabetic smokers who quit with varenicline showed no weight gain, improved cholesterol, and significantly increased GLP-1 and leptin levels over 4 months.

GLP-1 rose 16% after quitting
GLP-1 levels increased from 39.6 to 45.8 pM (p=0.016) after smoking cessation, suggesting improved incretin signaling without any GLP-1 medication

What the researchers found

After 3 months of varenicline-assisted smoking cessation in patients with T2DM/prediabetes, the 32 successful quitters showed no significant weight gain, no worsening of glycemic control, and significant improvements in lipid profile (total cholesterol 168→156 mg/dL, p=0.013; LDL 96→83 mg/dL, p=0.013). GLP-1 levels rose significantly (39.6→45.8 pM, p=0.016) and leptin increased (11→13.8 ng/dL, p=0.004). Physical activity also increased, with moderate-intensity activity participation rising from 28% to 56% (p=0.039).

Why it matters

Fear of weight gain is one of the biggest barriers to smoking cessation in people with diabetes, where extra weight could worsen blood sugar control. This study provides reassuring evidence that quitting with varenicline doesn't cause weight gain or glycemic deterioration in this population, and the significant rise in GLP-1 — a peptide that regulates appetite and insulin — suggests a favorable metabolic shift that may help explain why weight stayed stable.

How the study worked

Prospective observational study enrolling 53 patients with T2DM or prediabetes in a smoking cessation program. Thirty-two successfully quit after a 3-month course of varenicline and were followed for an additional month off medication. Measurements at baseline, 2.5 months, and 4 months included body weight, blood pressure, resting metabolic rate, HbA1c, fasting glucose, lipids, CRP, appetite-related hormones (leptin, GLP-1), and self-reported physical activity.

What this study cannot tell us

Small sample size (32 successful quitters analyzed), no control group, and short follow-up (4 months total). The observational design cannot separate the effects of varenicline from the effects of smoking cessation itself on metabolic parameters. Self-reported physical activity is subject to bias. Longer follow-up would be needed to determine whether the metabolic benefits and weight stability persist.

How to read the evidence

This is a small prospective observational study without a control group. While it demonstrates meaningful associations with statistical significance, the lack of randomization and small sample size (32 quitters) limit the strength of causal conclusions.

When this study was published

Published in 2024 with recent data collection, this study is current and relevant to ongoing clinical discussions about smoking cessation strategies in metabolic disease.

The bigger picture

GLP-1 is the same peptide targeted by blockbuster obesity and diabetes drugs like semaglutide and tirzepatide. The finding that smoking cessation naturally raises GLP-1 levels is notable — it suggests that quitting smoking may activate some of the same beneficial metabolic pathways that these medications target pharmacologically. This adds a peptide-biology dimension to the well-established cardiovascular and metabolic benefits of smoking cessation in diabetes.

Questions still open

Is the rise in endogenous GLP-1 after smoking cessation a direct effect of removing nicotine's suppression of GLP-1 secretion, or an indirect result of dietary and activity changes?
Would combining smoking cessation with GLP-1 receptor agonist therapy provide additive metabolic benefits and further prevent post-cessation weight gain?
Do the GLP-1 and leptin increases persist beyond the 4-month observation period, or do they normalize over time?

Common questions

Will I gain weight if I quit smoking with diabetes?

This study found that diabetic and prediabetic patients who quit smoking with varenicline did not gain significant weight over 4 months. Their cholesterol actually improved, blood sugar control stayed stable, and levels of GLP-1 (a peptide that helps regulate appetite and insulin) increased. While larger studies are needed, these findings challenge the common fear that quitting smoking inevitably leads to weight gain in diabetes.

Why did GLP-1 levels rise after quitting smoking?

The exact mechanism isn't fully established, but smoking and nicotine are known to affect gut hormone secretion. When patients quit, the removal of nicotine's influence on the digestive system may allow GLP-1-producing cells to function more effectively. Changes in diet and increased physical activity after quitting could also contribute to higher GLP-1 release.

Read the original research

Metabolic Changes Following Smoking Cessation in Patients with Type 2 Diabetes Mellitus.

Biomedicines, 12(8)

View on PubMed ↗Publisher’s paper ↗

Citation

Driva, Stamatina; Korkontzelou, Aliki; Tonstad, Serena; Tentolouris, Nikolaos; Litsiou, Eleni; Vasileiou, Vasiliki; Vassiliou, Alice G; Saltagianni, Vassiliki; Katsaounou, Paraskevi. (2024). Metabolic Changes Following Smoking Cessation in Patients with Type 2 Diabetes Mellitus.. Biomedicines, 12(8). https://doi.org/10.3390/biomedicines12081882