Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF, et al.
JAMA. Date of publication 2016 Jul 19;volume 316(3):313-24.
1. JAMA. 2016 Jul 19;316(3):313-24. doi: 10.1001/jama.2016.9400.
Comparison of Clinical Outcomes and Adverse Events Associated With
Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.
Palmer SC(1), Mavridis D(2), Nicolucci A(3), Johnson DW(4), Tonelli M(5), Craig
JC(6), Maggo J(1), Gray V(1), De Berardis G(3), Ruospo M(7), Natale P(8),
Saglimbene V(8), Badve SV(9), Cho Y(10), Nadeau-Fredette AC(11), Burke M(4),
Faruque L(12), Lloyd A(13), Ahmad N(13), Liu Y(13), Tiv S(13), Wiebe N(13),
Strippoli GF(14).
Author information:
(1)Department of Medicine, University of Otago Christchurch, Christchurch, New
Zealand.
(2)Department of Primary Education, School of Education, University of Ioannina,
University Campus, Dourouti, Ioannina, Greece3Department of Hygiene and
Epidemiology, School of Health Sciences, University of Ioannina, University
Campus, Dourouti, Ioannina, G.
(3)Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara,
Italy.
(4)Division of Medicine, Department of Renal Medicine, University of Queensland
at the Princess Alexandra Hospital, Woolloongabba, Australia6Translational
Research Institute, University of Queensland, Woolloongabba, Australia.
(5)Cumming School of Medicine, Health Sciences Centre, University of Calgary,
Foothills Campus, Calgary, Alberta, Canada.
(6)Sydney School of Public Health, University of Sydney, Sydney, Australia.
(7)Division of Nephrology and Transplantation, Department of Translational
Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy10Diaverum
Medical Scientific Office, Lund, Sweden.
(8)Diaverum Medical Scientific Office, Lund, Sweden.
(9)Division of Medicine, Department of Renal Medicine, University of Queensland
at the Princess Alexandra Hospital, Woolloongabba, Australia11The George
Institute for Global Health, Sydney, Australia.
(10)Division of Medicine, Department of Renal Medicine, University of Queensland
at the Princess Alexandra Hospital, Woolloongabba, Australia.
(11)Nephrology Division, Department of Medicine, University of Montreal,
Montreal, Quebec, Canada.
(12)Department of Medicine, Royal Alexandra Hospital, Edmonton, Alberta, Canada.
(13)Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
(14)Sydney School of Public Health, University of Sydney, Sydney,
Australia10Diaverum Medical Scientific Office, Lund, Sweden15Department of
Emergency and Organ Transplantation, University of Bari, Bari, Italy.
Comment in
Evid Based Med. 2016 Dec;21(6):224.
IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes.
OBJECTIVE: To estimate the relative efficacy and safety associated with
glucose-lowering drugs including insulin.
DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE,
and EMBASE databases through March 21, 2016.
STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration.
DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis.
MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality.
Secondary outcomes included all-cause mortality, serious adverse events,
myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure
(rescue treatment or lack of efficacy), hypoglycemia, and body weight.
RESULTS: A total of 301 clinical trials (1,417,367 patient-months) were included;
177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030
patients) of drugs added to metformin (dual therapy); and 29 trials (10,598
patients) of drugs added to metformin and sulfonylurea (triple therapy). There
were no significant differences in associations between any drug class as
monotherapy, dual therapy, or triple therapy with odds of cardiovascular or
all-cause mortality. Compared with metformin, sulfonylurea (standardized mean
difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95%
CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and
α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were
associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI,
2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin
(OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated
with greatest odds of hypoglycemia. When added to metformin, drugs were
associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest
odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]).
When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated
with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10%
[95% CI, -18% to -2%]).
CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no
significant differences in the associations between any of 9 available classes of
glucose-lowering drugs (alone or in combination) and the risk of cardiovascular
or all-cause mortality. Metformin was associated with lower or no significant
difference in HbA1C levels compared with any other drug classes. All drugs were
estimated to be effective when added to metformin. These findings are consistent
with American Diabetes Association recommendations for using metformin
monotherapy as initial treatment for patients with type 2 diabetes and selection
of additional therapies based on patient-specific considerations.
DOI: 10.1001/jama.2016.9400
PMID: 27434443 [Indexed for MEDLINE]
