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Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes

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Clar, C., Gill, J. A. (James Alexander), Court, Rachel A. and Waugh, Norman. (2012) Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open, Vol.2 (No.5). e001007. ISSN 2044-6055

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Abstract

Background Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents.

Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.

Data sources MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers.

Inclusion criteria Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy.

Methods Systematic review. Quality assessment used the Cochrane risk of bias score.

Results Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo).

Limitations Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers.

Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Warwick Evidence
Faculty of Medicine > Warwick Medical School > Health Sciences
Library of Congress Subject Headings (LCSH): Non-insulin-dependent diabetes -- Treatment
Journal or Publication Title: BMJ Open
Publisher: BMJ
ISSN: 2044-6055
Official Date: 2012
Volume: Vol.2
Number: No.5
Page Range: e001007
Identification Number: 10.1136/bmjopen-2012-001007
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
References:

1. Diabetes UK. Diabetes in the UK: key statistics on diabetes. http://
www.diabetes.org.uk/Documents/Reports/
Diabetes_in_the_UK_2010.pdf. 2010. (accessed 2 Aug 2012).
2. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity,
diabetes, and obesity-related health risk factors, 2001. JAMA
2003;289:76–9.
3. Stone PH, Muller JE, Hartwell T, et al. The effect of diabetes mellitus
on prognosis and serial left ventricular function after acute
myocardial infarction: contribution of both coronary disease and
diastolic left ventricular dysfunction to the adverse prognosis. The
MILIS Study Group. J Am Coll Cardiol 1989;14:49–57.
4. Santer R, Kinner M, Lassen CL, et al. Molecular analysis of the
SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol
2003;14:2873–82.
5. Hanefeld M, Forst T. Dapagliflozin, an SGLT2 inhibitor, for diabetes.
Lancet 2010;375:2196–8.
6. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews
of Interventions Version 5.1.0 (updated March 2011). 2011. The
Cochrane Collaboration. (accessed 9 Aug 2012).
7. WHO. Definition, diagnosis and classification of diabetes mellitus
and its complications: report of a WHO consultation. WHO/NCD/
NCS/99.2. 1999. http://whqlibdoc.who.int/hq/1999/who_ncd_ncs_99.
2.pdf. (accessed 9 Aug 2012).
8. Bailey CJ, Gross JL, Pieters A, et al. Effect of dapagliflozin in
patients with type 2 diabetes who have inadequate glycaemic control
with metformin: a randomised, double-blind, placebo-controlled trial.
Lancet 2010;375:2223–33.
9. Bolinder J, Ljunggren O, Kullberg J, et al. Effects of dapagliflozin on
body weight, total fat mass, and regional adipose tissue distribution
in patients with type 2 diabetes mellitus with inadequate glycemic
control on metformin. J Clin Endocrinol Metab 2012;97:1020–31.
10. Ljunggren O, Bolinder J, Johansson L, et al. Dapagliflozin has no
effect on markers of bone formation and resorption or bone mineral
density in patients with inadequately controlled type 2 diabetes
mellitus on metformin. Diabetes Obes Metab 2012;14:990–9.
11. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus
glipizide as add-on therapy in patients with type 2 diabetes who
have inadequate glycemic control with metformin: a randomized,
52-week, double-blind, active-controlled noninferiority trial. Diabetes
Care 2011;34:2015–22.
12. Rosenstock J, Vico M, Wei L, et al. Effects of dapagliflozin, an
SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in
patients with type 2 diabetes inadequately controlled on pioglitazone
monotherapy. Diabetes Care 2012;35:1473–8.
13. Strojek K, Yoon KH, Hruba V, et al. Effect of dapagliflozin in patients
with type 2 diabetes who have inadequate glycaemic control with
glimepiride: a randomized, 24-week, double-blind, placebo-controlled
trial. Diabetes Obes Metab 2011;13:928–38.
14. Wilding JP, Norwood P, T’joen C, et al. A study of dapagliflozin in
patients with type 2 diabetes receiving high doses of insulin plus
insulin sensitizers: applicability of a novel insulin-independent
treatment. Diabetes Care 2009;32:1656–62.
15. Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of
dapagliflozin in patients with type 2 diabetes mellitus receiving high
doses of insulin: a randomized trial. Ann Intern Med
2012;156:405–15.
16. Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of
canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on
to metformin in subjects with type 2 diabetes. Diabetes Care
2012;35:1232–8.
17. Komoroski B, Vachharajani N, Boulton D, et al. Dapagliflozin, a
novel SGLT2 inhibitor, induces dose-dependent glucosuria in
healthy subjects. Clin Pharmacol Ther 2009;85:520–6.
18. Del Prato S, Nauck MA, Rohwedder K, et al. Long-term efficacy and
safety of dapagliflozin vs add-on glipizide in patients with type 2
diabetes inadequately controlled with metformin: 2 year results.
A 47th Annual Meeting of the European Association for the Study of
Diabetes 2011; Lisbon, Portugal. S348.
19. Wilding J, Woo V, Rohwedder K, et al. Long-term effectiveness of
dapagliflozin over 104 weeks in patients with type 2 diabetes poorly
controlled with insulin. A 72nd Scientific Session of the American
Diabetes Association 2012; Philadelphia, USA. A267–8.
20. Waugh N, Cummins E, Royle P, et al. Newer agents for blood
glucose control in type 2 diabetes: systematic review and economic
evaluation. Health Technol Assess 2010;14:1–248.
21. Musso G, Gambino R, Cassader M, et al. A novel approach to
control hyperglycemia in type 2 diabetes: sodium glucose
co-transport (SGLT) inhibitors: systematic review and meta-analysis
of randomized trials. Ann Med 2012;44:375–93.
22. Food and Drug Administration. Summary minutes of the endocronologic
and metabolic drugs advisory committee. 2011. http://www.fda.gov/
downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/
EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262990.pdf.
(accessed 9 Aug 2012).
URI: http://wrap.warwick.ac.uk/id/eprint/51186

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