Tools for Practice Outils pour la pratique

#180 GLP-1 Analogues in Diabetes: As sweet as can be?

Do glucagon-like peptide 1 analogues (GLP-1) improve patient-oriented outcomes in type 2 diabetes?

Compared to placebo, semaglutide and liraglutide, but not lixisenatide, reduce cardiovascular disease (CVD) for ~1 in 50 diabetics with existing CVD over 2-4 years, irrespective of specific A1c targets (attaining ~7.5%). These drugs reduce weight 0.7-4.3 kg, but around one in 25 more than placebo will stop due to gastrointestinal effects. Some uncertainty around neoplasm risk remains.

CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session

Three randomized controlled trials (RCTs), mean age 60-65, diabetic 9-14 years, >80% past CVD. All GLP-1 subcutaneous versus placebo. Statistically significant results:
  • Liraglutide (1.8 mg daily): 9,340 patients x 3.8 years:1
    • A1c from 8.7% to: ~7.7% liraglutude versus 8.1% placebo.
    • CVD: 13% versus 14.9%, Number Needed to Treat (NNT)=53.
    • Mortality: NNT=72.
    • Harms: Gallbladder disease, Number Needed to Harm (NNH)=83.
  • Semaglutide (0.5 or 1 mg weekly; pooled): 3,297 patients x 2.1 years:2
    • A1c from 8.7% to: 7.3-7.6% semaglutide versus 8.3% placebo.
    • CVD: 6.6% versus 8.9%, NNT=44.
    • Mortality: No difference.
    • Harms: Retinopathy, NNH=83.
  • Lixisenatide (20 mcg daily): 6,068 patients x 2.1 years:3
    • A1c from 7.6% to: ~7.3% lixisenatide versus ~7.6% placebo.
    • CVD or mortality: No difference.
  • Other findings: Weight loss (0.7-4.3 kg), reduced nephropathy (NNT=67-98; not lixisenatide), hypoglycemia no different or lower.
    • More discontinued due to gastrointestinal irritation (NNH=16-33).
  • Neoplasm (benign/malignant) numerically higher with GLP-1 agonist in each study.1-3
    • Meta-analyses (missing above liraglutide and semaglutide RCTs): No cancer risk.4,5
      • Except high-quality liraglutide RCTs, odds ratio=2.60 (1.08-6.27).5
    • BMJ investigation questioned whether safety adequately evaluated.6
    • 2014 FDA/EMA review “had not reached a final conclusion” on causality between incretins and (specifically) pancreatic cancer, despite indicating concerns were not consistent with evidence.7
  • Clinicians should prioritize patient-oriented outcomes (like CVD) rather than sugars or microalbuminuria.
  • Large RCTs of DPP-4 medications demonstrate no effect on CVD and minimal to no effect on microvascular outcomes.8
  • Liraglutide is the only GLP-1 agonist available in Canada with a large CVD trial (others: dulaglutide and exenatide), costs ~$185/month and while often covered by private insurance, it is not covered by public insurance plans outside of Quebec.

Latest Tools for Practice
Derniers outils pour la pratique

#367 Oral Calcitonin Gene-related Peptide Antagonists: A painfully long name for the acute treatment of migraines

What are the risks and benefits of ubrogepant for the acute treatment of episodic migraines?
Read Lire 0.25 credits available Crédits disponibles

#366 Looking for Closure: Managing simple excisions or wounds efficiently

What are some options for efficiency in wound closure?
Read Lire 0.25 credits available Crédits disponibles

#365 Shrooms for Glooms: Evidence for psilocybin for depression

What are the benefits and harms of psilocybin for treatment-resistant/recurrent depression?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session

  • Adrienne J Lindblad BSP ACPR PharmD
  • G. Michael Allan MD CCFP

1. Marso SP, Daniels GH, Brown-Frandsen K, et al. N Engl J Med. 2016; 375:311-22.

2. Marso SP, Bain SC, Consoli A, et al. N Engl J Med. 2016; 375(10):1834-44.

3. Pfeffer MA, Claggett B, Diaz R, et al. N Engl J Med. 2015; 373:2247-57.

4. Chen H, Zhou X, Chen T, et al. Diabetes Ther. 2016; 7(4):725-42.

5. Alves C, Batel-Marques F, Macedo AF. Diabetes Res Clin Pract. 2012 Nov; 98(2):271-84.

6. Cohen D. BMJ. 2013; 346:f3680.

7. Egan AG, Blind E, Dunder K, et al. New Engl J Med. 2014; 370:794-7.

8. Barry A, Allan GM. Tools for Practice. Available at: Last accessed: January 18, 2017.

Authors have no conflicts of interest to declare.