Skip to main content
Top
Published in: Current Diabetes Reports 12/2019

01-12-2019 | Ramipril | Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)

Pharmacologic Randomized Clinical Trials in Prevention of Type 2 Diabetes

Authors: William C. Knowler, Jill P. Crandall

Published in: Current Diabetes Reports | Issue 12/2019

Login to get access

Abstract

Purpose of Review

There have been many randomized clinical trials testing lifestyle and drug interventions to prevent the development of type 2 diabetes in nondiabetic adults at high risk of the disease. We review the major trials using pharmacologic interventions with the primary outcome of preventing diabetes. The trials are grouped according to the main mechanism by which the drugs were thought to have the potential for preventing diabetes.

Recent Findings

Drugs in several different classes have been effective in reducing the incidence of diabetes, but evidence for other long-term benefits, such as avoidance of complications and reducing mortality rates, is very limited.

Summary

Both drugs and lifestyle interventions are effective in preventing and delaying the onset of type 2 diabetes in high-risk adults. The choices of what drugs to use and when during the development of type 2 diabetes to introduce them are not clear.
Literature
1.
go back to reference Knowler WC, Crandall JP, Chiasson J-L, Nathan DM. Prevention of type 2 diabetes. In: CS CCC, Menke A, Cissell MA, Eberhardt MS, Meigs JB, Gregg EW, Knowler WC, Barrett-Connor E, Becker DJ, Brancati FL, Boyko EJ, Herman WH, Howard BV, KMV N, Rewers M, Fradkin JE, editors. Diabetes in America, 3rd ed. Vol NIH Pub No. 17-1468. Bethesda, MD: National Institutes of Health; 2018. p. 38–1. to 38-21. Knowler WC, Crandall JP, Chiasson J-L, Nathan DM. Prevention of type 2 diabetes. In: CS CCC, Menke A, Cissell MA, Eberhardt MS, Meigs JB, Gregg EW, Knowler WC, Barrett-Connor E, Becker DJ, Brancati FL, Boyko EJ, Herman WH, Howard BV, KMV N, Rewers M, Fradkin JE, editors. Diabetes in America, 3rd ed. Vol NIH Pub No. 17-1468. Bethesda, MD: National Institutes of Health; 2018. p. 38–1. to 38-21.
4.
go back to reference Keen H, Jarrett RJ, McCartney P. The ten-year follow-up of the Bedford survey (1962-1972): glucose tolerance and diabetes. Diabetologia. 1982;22(2):73–8.CrossRefPubMed Keen H, Jarrett RJ, McCartney P. The ten-year follow-up of the Bedford survey (1962-1972): glucose tolerance and diabetes. Diabetologia. 1982;22(2):73–8.CrossRefPubMed
8.
go back to reference Jarrett RJ, Keen H, Fuller JH, McCartney M. Worsening to diabetes in men with impaired glucose tolerance (“borderline diabetes”). Diabetologia. 1979;16(1):25–30.CrossRefPubMed Jarrett RJ, Keen H, Fuller JH, McCartney M. Worsening to diabetes in men with impaired glucose tolerance (“borderline diabetes”). Diabetologia. 1979;16(1):25–30.CrossRefPubMed
12.
16.
go back to reference Heymsfield SB, Segal KR, Hauptman J, Lucas CP, Boldrin MN, Rissanen A, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000;160(9):1321–6.CrossRefPubMed Heymsfield SB, Segal KR, Hauptman J, Lucas CP, Boldrin MN, Rissanen A, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000;160(9):1321–6.CrossRefPubMed
18.
go back to reference Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297–308. https://doi.org/10.3945/ajcn.111.024927.CrossRefPubMed Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297–308. https://​doi.​org/​10.​3945/​ajcn.​111.​024927.CrossRefPubMed
24.
go back to reference • Holman RR, Coleman RL, Chan JCN, et al. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(11):877–86. https://doi.org/10.1016/S2213-8587(17)30309-1. This RCT in an Asian population with IGT showed that acarbose reduced incident diabetes by 18% , but failed to confirm the reduction in cardiovascular risk that had been reported from the earlier STOP-NIDDM trial. CrossRefPubMed • Holman RR, Coleman RL, Chan JCN, et al. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(11):877–86. https://​doi.​org/​10.​1016/​S2213-8587(17)30309-1. This RCT in an Asian population with IGT showed that acarbose reduced incident diabetes by 18% , but failed to confirm the reduction in cardiovascular risk that had been reported from the earlier STOP-NIDDM trial. CrossRefPubMed
35.
go back to reference Rosenstock J, Foley JE, Rendell M, Landin-Olsson M, Holst JJ, Deacon CF, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care. 2008;31(1):30–5. https://doi.org/10.2337/dc07-1616.CrossRefPubMed Rosenstock J, Foley JE, Rendell M, Landin-Olsson M, Holst JJ, Deacon CF, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care. 2008;31(1):30–5. https://​doi.​org/​10.​2337/​dc07-1616.CrossRefPubMed
36.
go back to reference Hemmingsen B, Sonne DP, Metzendorf MI, Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2017;5:CD012204.PubMed Hemmingsen B, Sonne DP, Metzendorf MI, Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2017;5:CD012204.PubMed
39.
go back to reference • Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med. 2019;381(6):520–30. https://doi.org/10.1056/NEJMoa1900906. Although many observational studies have demonstated an association between diabetes risk and vitamin D deficiency, this large RCT showed that high dose vitamin D (4000 IU daily) supplementation did not reduce incident diabetes in a cohort with prediabetes. CrossRefPubMedPubMedCentral • Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med. 2019;381(6):520–30. https://​doi.​org/​10.​1056/​NEJMoa1900906. Although many observational studies have demonstated an association between diabetes risk and vitamin D deficiency, this large RCT showed that high dose vitamin D (4000 IU daily) supplementation did not reduce incident diabetes in a cohort with prediabetes. CrossRefPubMedPubMedCentral
48.
go back to reference •• Diabetes Prevention Program Research Group. Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the diabetes prevention program and diabetes prevention program outcomes study. Diabetes Care. 2019;42(4):601–8. https://doi.org/10.2337/dc18-1970. In this long-term follow-up of the Diabetes Prevention Program, participants in the metformin treatment arm had durable reduction in diabetes risk over 15 years. The greatest benefit was observed among individuals with higher baseline fasting glucose or HbA 1c and women with a history of GDM. CrossRefPubMedCentral •• Diabetes Prevention Program Research Group. Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the diabetes prevention program and diabetes prevention program outcomes study. Diabetes Care. 2019;42(4):601–8. https://​doi.​org/​10.​2337/​dc18-1970. In this long-term follow-up of the Diabetes Prevention Program, participants in the metformin treatment arm had durable reduction in diabetes risk over 15 years. The greatest benefit was observed among individuals with higher baseline fasting glucose or HbA 1c and women with a history of GDM. CrossRefPubMedCentral
Metadata
Title
Pharmacologic Randomized Clinical Trials in Prevention of Type 2 Diabetes
Authors
William C. Knowler
Jill P. Crandall
Publication date
01-12-2019
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 12/2019
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-019-1268-5

Other articles of this Issue 12/2019

Current Diabetes Reports 12/2019 Go to the issue

Diabetes and Pregnancy (M-F Hivert and CE Powe, Section Editors)

Diagnostic Strategies for Gestational Diabetes Mellitus: Review of Current Evidence

Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)

Human Endogenous Retroviruses and Type 1 Diabetes

Immunology, Transplantation, and Regenerative Medicine (L Piemonti and V Sordi, Section Editors)

Organoids from the Human Fetal and Adult Pancreas

Health Care Delivery Systems and Implementation in Diabetes (ME McDonnell and AR Sadhu, Section Editors)

mHealth Interventions for Disadvantaged and Vulnerable People with Type 2 Diabetes

Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors)

Diabetic Gastroparesis and Glycaemic Control

Therapies and New Technologies in the Treatment of Diabetes (M Pietropaolo, Section Editor)

Bariatric Surgery in the Treatment of Type 2 Diabetes

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.