Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes a meta-analysis

Palmer, Suetonia C., Mavridis, Dimitris, Nicolucci, Antonio, Johnson, David W., Tonelli, Marcello, Craig, Jonathan C., Maggo, Jasjot, Gray, Vanessa, De Berardis, Giorgia, Ruospo, Marinella, Natale, Patrizia, Saglimbene, Valeria, Badve, Sunil V., Cho, Yeoungjee, Nadeau-Fredette, Annie-Claire, Burke, Michael, Faruque, Labib, Lloyd, Anita, Ahmad, Nasreen, Liu, Yuanchen, Tiv, Sophanny, Wiebe, Natasha and Strippoli, Giovanni F. M. (2016) Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes a meta-analysis. JAMA: The Journal of the American Medical Association, 316 3: 313-324. doi:10.1001/jama.2016.9400


Author Palmer, Suetonia C.
Mavridis, Dimitris
Nicolucci, Antonio
Johnson, David W.
Tonelli, Marcello
Craig, Jonathan C.
Maggo, Jasjot
Gray, Vanessa
De Berardis, Giorgia
Ruospo, Marinella
Natale, Patrizia
Saglimbene, Valeria
Badve, Sunil V.
Cho, Yeoungjee
Nadeau-Fredette, Annie-Claire
Burke, Michael
Faruque, Labib
Lloyd, Anita
Ahmad, Nasreen
Liu, Yuanchen
Tiv, Sophanny
Wiebe, Natasha
Strippoli, Giovanni F. M.
Title Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes a meta-analysis
Journal name JAMA: The Journal of the American Medical Association   Check publisher's open access policy
ISSN 1538-3598
0098-7484
Publication date 2016-07-19
Year available 2016
Sub-type Article (original research)
DOI 10.1001/jama.2016.9400
Open Access Status Not yet assessed
Volume 316
Issue 3
Start page 313
End page 324
Total pages 12
Place of publication Chicago, IL, United States
Publisher American Medical Association
Collection year 2017
Language eng
Formatted abstract
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 (1417367 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.
Keyword Glucose-lowering drugs
Type 2 diabetes
Adults
Disability
Mortality
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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