PRESERVE-β
Abstract
OBJECTIVE—To compare long-term efficacy and safety of initial combination therapy with nateglinide/metformin versus glyburide/metformin. RESEARCH DESIGN AND METHODS—We conducted a randomized, multicenter, double-masked, 2-year study of 428 drug-naïve patients with type 2 diabetes. Patients received 120 mg a.c. nateglinide or 1.25 mg q.d. glyburide plus 500 mg q.d. open-label metformin for the initial 4 weeks. During a subsequent 12-week titration period, glyburide and metformin were increased by 1.25- and 500-mg increments to maximum daily doses of 10 and 2,000 mg, respectively, if biweekly fasting plasma glucose (FPG) ≥6.7 mmol/l. Nateglinide was not titrated. Blinding was maintained by use of matching placebo for nateglinide and glyburide. An 88-week monitoring period followed, during which HbA1c (A1C), FPG, and postprandial glucose excursions (PPGEs) during an oral glucose tolerance test were measured. RESULTS—In nateglinide/metformin-treated patients, mean A1C was 8.4% at baseline and 6.9% at week 104. In glyburide/metformin-treated patients, mean A1C was 8.3% at baseline and 6.8% at week 104 (P < 0.0001 vs. baseline for both treatments, NS between treatments). The ΔPPGE averaged −96 ± 19 (P < 0.0001) and −57 ± 22 mmol · l−1 · min−1 (P < 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas ΔFPG was –1.6 ± 0.2 (P < 0.0001) and −2.4 ± 0.2 mmol/l (P < 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P < 0.01 between groups). Thus, the two treatments achieved similar efficacy with differential effects on FPG versus PPGE. Hypoglycemia occurred in 8.2 and 17.7% of patients receiving nateglinide/metformin and glyburide/metformin, respectively. CONCLUSIONS—Similar good glycemic control can be maintained for 2 years with either treatment regimen, but nateglinide/metformin may represent a safer approach to initial combination therapy.
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The risk of weight gain with glinides is similar to that for sulfonylureas, but hypoglycemia may be less frequent, at least with nateglinide, than with some sulfonylureas.
“The risk of weight gain is similar to that for the sulfonylureas, but hypoglycemia may be less frequent, at least with nateglinide, than with some sulfonylureas (58,59).”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [58]
Nateglinide is somewhat less effective in lowering A1C than repaglinide when used as monotherapy or in combination therapy.
“Nateglinide is somewhat less effective in lowering A1C than repaglinide when used as monotherapy or in combination therapy (57,58).”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [58]
Combinations of metformin and insulin secretagogue can reduce HbA1c between 1.5% and 2.2% in patients sub-optimally controlled by diet and exercise.
“Combinations of metformin and insulin secretagogue can reduce HbA1c between 1.5% to 2.2% in patients sub-optimally controlled by diet and exercise [21].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [21]
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- Authors
- Gerich, J., Raskin, P., Jean-Louis, L., Purkayastha, D., & Baron, M. A.
- Affiliations
- University of Rochester Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- Clinical Development and Medical Affairs, Novartis Pharmaceuticals, East Hanover, New Jersey
- Biometrics Medical Affairs, Novartis Pharmaceuticals, East Hanover, New Jersey
- ORCID
- Baron, Michelle A.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2005-09-01
- Volume
- 28
- Issue
- 9
- Pages
- 2093-2099
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2132389483
- Cited by
- 116
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2019: 4 · 2018: 8 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 14 · 2012: 12
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, nateglinide, glibenclamide, metformin, combination therapy, initial treatment, glycemic control, HbA1c, postprandial glucose excursions, fasting blood glucose, hypoglycemia, sulfonylureas, thiazolidinediones, long-term efficacy and safety, drug-naive patients, oral glucose tolerance
- MeSH terms
- Nateglinide, Cyclohexanes, Diabetes Mellitus, Type 2, Drug Administration Schedule, Drug Therapy, Combination, Female, Glyburide, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Phenylalanine, Placebos, Body Mass Index
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