- The Use of GLP-1 Receptor Agonists is Associated with an Increased Risk of Thyroid Cancer
- Checking for H. Pylori and Eradicating it May Protect Against Peptic Ulcer Bleed Before Prescribing Aspirin
- Long-Term Use of PPIs in Type 2 Diabetics is Associated with an Increased Risk of Cardiovascular Disease
1. The Use of GLP-1 Receptor Agonists is Associated with an Increased Risk of Thyroid Cancer
OBJECTIVE: To determine whether use of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) is associated with increased risk of thyroid cancer.
RESEARCH DESIGN AND METHODS: A nested case-control analysis was performed with use of the French national health care insurance system (SNDS) database. Individuals with type 2 diabetes treated with second-line antidiabetes drugs between 2006 and 2018 were included in the cohort. All thyroid cancers were identified through hospital discharge diagnoses and medical procedures between 2014 and 2018. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as current use and cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Case subjects were matched with up to 20 control subjects on age, sex, and length of diabetes with the risk-set sampling procedure. Risk of thyroid cancer related to use of GLP-1 RA was estimated with a conditional logistic regression with adjustment for goiter, hypothyroidism, hyperthyroidism, other antidiabetic drugs, and social deprivation index.
RESULTS: A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1–3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27–1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04–3.05).
CONCLUSIONS: In the current study we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1–3 years of treatment.
Bezin J, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care 2023;46(2):384–390
2. Checking for H. Pylori and Eradicating it May Protect Against Peptic Ulcer Bleed Before Prescribing Aspirin
BACKGROUND: Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding.
METHODS: We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96.
FINDINGS: Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9–6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41–2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62–4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14–0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55–3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients).
INTERPRETATION: H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term.
FUNDING: National Institute for Health and Care Research Health Technology Assessment.
Hawkey C, et al. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022; 400(10363):1597-1606.
3. Long-Term Use of PPIs in Type 2 Diabetics is Associated with an Increased Risk of Cardiovascular Disease
BACKGROUND: Proton pump inhibitors (PPIs) are widely used drugs for gastric-acid-related diseases, which may have an impact on the gut microbiome. We aimed to evaluate the associations of PPI use with risks of cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D).
METHODS: We analysed the associations of PPI use with risks of coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality in 19,229 adults with T2D using data from the UK Biobank study.
RESULTS: During a median follow-up of 10.9-11.2 years, we documented a total of 2,971 CAD, 1,827 MI, 1,192 HF, and 738 stroke cases, along with 2,297 total deaths. PPI use was significantly associated with higher risks of CAD (HR, 1.27; 95% CI, 1.15-1.40), MI (HR, 1.34; 95% CI, 1.18-1.52), HF (HR, 1.35; 95% CI, 1.16-1.57) and all-cause mortality (HR, 1.30; 95% CI, 1.16-1.45). No significant association was observed between PPI use and stroke (HR, 1.11; 95% CI, 0.90-1.36). The results were consistent in the subgroup analyses stratified by factors including indications of PPI, anti-diabetic medication use, and antiplatelet drug use. Analyses in a 1:1 propensity score-matched cohort of PPI users versus non-users yielded similar results.
INTERPRETATION: Our data suggested that PPI use was associated with higher risks of CVD events and mortality among patients with T2D. The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced.
Geng Tingting, et al. Proton Pump Inhibitor Use and Risks of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes. J Clin Endocrinol Metab. 2022 Dec 27;dgac750. doi: 10.1210/clinem/dgac750. Online ahead of print.