In short Article

Prolonged-release Metformin

Presumed advantage not confirmed


Metformin, Glucient® SR (Consilient Health), prolonged-release tablets 500, 750 and 1000 mg
In theory, prolonged-release metformin as a diabetes drug should cause fewer gastro-intestinal adverse effects than metformin without prolonged release. This is, however, not convincingly proven by research studies. The manufacturer of Glucient® SR previously claimed on its website that prolonged-release metformin has ‘a favourable gastrointestinal profile’, a claim which was based on low-quality studies. Interestingly, the manufacturer has since removed this claim from its website, possibly because they realised that the evidence was very meagre. This is also made clear by this Ge-Bu article. The registration procedure for Glucient® SR did not include the adverse effects profile as an evaluation criterion. What remains of the presumed advantages of prolonged-release metformin is its ease of use for patients with diabetes (once a day dosage), which could imply greater compliance. However, the influence of this improved compliance on HbA1c values or on microvascular or macrovascular endpoints has not been investigated. Ge-Bu therefore rates prolonged-release metformin, which was recently authorised for the Dutch market, as ‘-’.


  • A new prolonged-release formulation of the diabetes drug metformin, claimed to have fewer gastrointestinal adverse effects, has recently been introduced on the Dutch market.
  • Research studies of fairly low quality show that there is no clear evidence that prolonged-release metformin does indeed have fewer gastrointestinal adverse effects than normal metformin.
  • Prolonged-release metformin is two to three times as expensive as normal metformin.
  • If gastrointestinal adverse effects arise, its dosage can be reduced, and patients can additionally be prescribed gliclazide.
  • If a patient does not tolerate metformin at all, they can switch to gliclazide.
  • In view of the lack of evidence to show that Glucient® SR provides added value compared to normal-release metformin, and in view of the higher costs, Ge-Bu rates this drug as ‘-’.

  1. Nederlands Huisartsen Genootschap. NHG-Standaard Diabetes mellitus type 2. Via: https://www.nhg.org/standaarden/volledig/nhg-standaard-diabetes-mellitus-type-2.
  2. Productinformatie Glucient®. CBG-MEB. Glucient SR 1000 mg. Via: https://db.cbg-meb.nl/ords/f?p=111:3::SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,NL,121455. Geraadpleegd op: 21-1-2019. 
  3. van Deventer K, Janssens HEJM. Klinische relevantie van onderzoeksuitkomsten - Wat schiet de patiënt ermee op? Ge-Bu 2019;53(1):1-11
  4. Fujioka K, Pans M, Joyal S. Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate-release metformin to a once-daily extended-release formulation. Clin Ther. 2003 Feb;25(2):515-29.
  5. Schwartz S, Fonseca V, Berner B, Cramer M, Chiang YK, Lewin A. Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes. Diabetes Care. 2006 Apr;29(4):759-64.
  6. Hameed M1, Khan K1, Salman S1, Mehmood N1 Dose Comparison And Side Effect Profile Of Metformin Extended Release Versus Metformin Immediate Release. J Ayub Med Coll Abbottabad. 2017 Apr-Jun;29(2):225-229.
  7. Derosa G, D'Angelo A, Romano D, Maffioli P. Effects of metformin extended release compared to immediate release formula on glycemic control and glycemic variability in patients with type 2 diabetes. Drug Des Devel Ther. 2017 May 16;11:1481-1488.
  8. Aggarwal N, Singla A, Mathieu C, Montanya E, Pfeiffer AFH, Johnsson E, Zhao J, Iqbal N, Bailey C. Metformin extended-release versus immediate-release: An international, randomized, double-blind, head-to-head trial in pharmacotherapy-naïve patients with type 2 diabetes. Diabetes Obes Metab. 2018 Feb;20(2):463–467. 
  9. Blonde L, Dailey GE, Jabbour SA, Reasner CA, Mills DJ. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Curr Med Res Opin. 2004 Apr;20(4):565-72.
  10. Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage® SR) in individuals intolerant to standard metformin — results from four UK centres . Br J Diabetes Vasc Dis. 2007 Sept/Oct;7(5):225-228
  11. Levy J, Cobas RA, Gomes MB. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus. Diabetol Metab Syndr. 2010 Mar 18;2:16.
  12. Derosa G, Romano D, Bianchi L, D’Angelo A, Maffioli P. Metformin powder formulation compared to metformin tablets on glycemic control and on treatment satisfaction in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2015;55(4):409-414.
  13. Donnelly LA, Morris AD, Pearson ER. Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study. Diabetes Obes Metab. 2009 Apr;11(4):338-42.
  14. Fatima M, Sadeeqa S, Nazir SU. Metformin and its gastrointestinal problems: A review. Biomedical Research. 2018;29(11):2285–9.

The literature refers to the Dutch text

Authors

  • mw D.M. Corbijn, BSc, mw drs M.A.E. Nieuwhof