Glycemia reduction in type 2 diabetes–microvascular and cardiovascular outcomes
Open accessAbstract
BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).
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In GRADE, no significant differences were found for major adverse cardiovascular events, hospitalization for HF, or cardiovascular death.
“although no significant differences were found for major adverse cardiovascular events, hospitalization for HF, or cardiovascular death (133).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [133]
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After Metformin — Next Steps for Type 2 Diabetes with Low Cardiovascular Risk
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Triglyceride glucose index as a biomarker for heart failure risk in H-type hypertension patients
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Trends in Use of Sulfonylurea Types Among US Adults with Diabetes: NHANES 1999–2020
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Duodenal mucosa resurfacing: the endoscopic silver bullet against metabolic disorders?
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The Main Diseases Related to Type 2 Diabetes Mellitus: A Scoping Review
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Pharmacologic Treatment of Obesity in the Context of Type 2 Diabetes
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Top studies of 2022 relevant to primary care
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The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes
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Roles of Empagliflozin in Diabetic Cardiomyopathy: A Review
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- Authors
- The GRADE Study Research Group
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- The GRADE Study Research Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-09-22
- Volume
- 387
- Issue
- 12
- Pages
- 1075-1088
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9832916
- OpenAlex
- W4296702407
- Cited by
- 159
- References
- 25
- Citations by year
- 2026: 22 · 2025: 39 · 2024: 42 · 2023: 51 · 2022: 5
- FWCI
- 25.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- Centers for Disease Control and Prevention
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34DK088043)
- American Diabetes Association
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, glycemic control, glucose-lowering medications, metformin, glargine, glimepiride, liraglutide, sitagliptin, microvascular complications, diabetic peripheral neuropathy, albuminuria, renal dysfunction, major adverse cardiovascular events, heart failure hospitalization, cardiovascular mortality, comparative effectiveness
- MeSH terms
- Sitagliptin Phosphate, Insulin Glargine, Liraglutide, Albuminuria, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Neuropathies, Drug Therapy, Combination, Glomerular Filtration Rate, Heart Failure, Glycated Hemoglobin, Humans, Hypertension, Hypoglycemic Agents, Metformin, Sulfonylurea Compounds, Diabetes Complications, Dyslipidemias, Microvessels, Comparative Effectiveness Research
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