GLP-1 Receptor Agonists: Research Updates
Thyroid Tumour Incidence
A retrospective cohort study of patients with type 2 diabetes and prior metformin use was conducted to analyse thyroid tumour incidence with initiation of a GLP-1 receptor agonist, versus those initiating use of sulfonylureas, dipeptidyl peptidase 4 inhibitors (DPP-4is), and sodium-glucose cotransporter 2 inhibitors (SGLT2is).
Findings
- No statistically significant increased risk of thyroid tumours was observed in the GLP-1 receptor agonist group (incidence ranged from 0.88 to 1.03 per 1,000 person-years), when compared to each of sulfonylureas, DPP-4is, and SGLT2is exposure groups.
- The authors stated that their conclusion did not change when a 1-year lag exposure period was used.
As tirzepatide was only recently available it was not included in the study.
Tirzepatide vs Semaglutide
The New England Journal of Medicine published a study comparing the change in weight over 72 weeks in adults with obesity, but without type 2 diabetes, receiving weekly tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg) subcutaneously. The study was funded by Eli Lilly (maker of tirzepatide) with therefore a risk of sponsorship bias. Also, participants were not blinded which can introduce further biases.
All participants in both groups received nutrition and physical activity counselling. Inclusion criteria included a BMI of ≥ 30 or a BMI of ≥ 27 and ≥ 1 prespecified obesity-related complication, and ≥ 1 reported unsuccessful dietary effort to lose weight. Exclusion criteria included use of a weight loss medication or GLP-1 receptor agonist within 90 days pre-screening.
Findings
| Change from baseline to week 72 | |||
| % Weight Change | Waist Circumference | Body Weight | |
| Tirzepatide | -20.1% | -18.4 cm | -22.8 kg |
| Semaglutide | -13.7% | -13.0 cm | -15.0 kg |
- Lipid levels, systolic and diastolic blood pressure, glycated hemoglobin, and fasting serum glucose all showed improvements in both treatment groups.
- Adverse gastrointestinal events were the most common adverse events in both groups and predominately arose with dose escalation (mostly mild to moderate in severity).
The use of semaglutide and tirzepatide are discussed in the Obesity in Adults module (November 2024) as treatment options.
Note: Tirzepatide injection (Zepbound KwikPenTM) was approved by Health Canada in May 2025 for obesity management.
Smoking Cessation Medications and Major Congenital Malformations
To evaluate the effect of prenatal use of smoking cessation medications (NRT, varenicline, and bupropion) on major congenital malformations (MCMs), a retrospective cohort study using data from 4 countries (Australia, New Zealand, Sweden, and Norway) was conducted and meta-analyses completed on the results. The base cohort included women (n=267,522) who smoked during their first trimester or were dispensed a smoking cessation medication within the first trimester or 90 days pre-conception. The data from 5.2 million births were included in the study, with a base cohort of 391,474 infants. Exclusions included multiple births, stillbirths, births lacking adequate information needed to estimate the date of conception, and MCMs due to genetic syndromes.
Findings
- The study results suggested no increased risk of MCMs overall with use of NRT, varenicline, or bupropion during the first trimester, compared with smoking.
- Several malformation subgroups had no evidence of greater risk with NRT or varenicline use, while risk for malformation subgroups could not be fully estimated for bupropion.
Long-term functional defects were not examined in the study.