Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes

Janka, Hans U.; Plewe, Gerd; Riddle, Matthew C.; Kliebe-Frisch, Christine; Schweitzer, Matthias A.; Yki-Järvinen, Hannele

doi:10.2337/diacare.28.2.254

Cited by 414Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes

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Janka, Hans U., Plewe, Gerd, Riddle, Matthew C., Kliebe-Frisch, Christine, Schweitzer, Matthias A., Yki-Järvinen, Hannele·2005·Diabetes Care

DOI 10.2337/diacare.28.2.254

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Abstract

OBJECTIVE—To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS—In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naïve patients with poor glycemic control (fasting blood glucose [FBG] ≥120 mg/dl, HbA1c 7.5–10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG ≤100 mg/dl (both insulins) and predinner blood glucose ≤100 mg/dl (70/30 only) using a weekly forced-titration algorithm. RESULTS—Mean HbA1c decrease from baseline was significantly more pronounced (−1.64 vs. −1.31%, P = 0.0003), and more patients reached HbA1c ≤7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference −17 mg/dl [–0.9 mmol/l], P < 0.0001), and more patients reached target FBG ≤100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001). CONCLUSIONS—Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.

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Basal insulin analogs reduce hypoglycemia risk compared with NPH insulin.
“Basal insulin analogs are preferred over NPH insulin because of a reduced risk of hypoglycemia.1066–1071”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1070]
The Hypoglycemia section reports fewer confirmed hypoglycemic episodes with glargine plus oral drugs than with twice-daily premixed 70/30 insulin, which contains NPH. The Conclusions clarify that the trial compared treatment regimens, not glargine directly against NPH alone; it therefore does not establish the claimed risk reduction for basal insulin analogs versus NPH insulin generally. (LLM, conf=0.88)
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Glargine was also associated with a lower frequency of hypoglycemia than premixed insulins.
“Glargine was also associated with a lower frequency of hypoglycemia than premixed insulins (136,137).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [136]

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Authors: Janka, H. U., Plewe, G., Riddle, M. C., Kliebe-Frisch, C., Schweitzer, M. A., & Yki-Järvinen, H.
Affiliations: Zentralkrankenhaus, Bremen-Nord, Bremen, Germany
Oregon Health & Science University (US)
ABEnzymes (Germany) (DE)
Department of Medicine, University of Helsinki, Helsinki, Finland
ORCID: Riddle, Matthew C.
Schweitzer, Matthias A.
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2005-02-01
Volume: 28
Issue: 2
Pages: 254-259
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/diacare.28.2.254
OpenAlex: W2121414237
Cited by: 414
References: 15
Citations by year: 2025: 1 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 9 · 2019: 13 · 2018: 14 · 2017: 7 · 2016: 15 · 2015: 29 · 2014: 25 · 2013: 29 · 2012: 18
FWCI: 30.99
Type: journal article
Language: en
Open access: bronze
doi.org
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: insulin glargine, basal insulin, premixed insulin, type 2 diabetes, oral antidiabetic drugs, glimepiride, metformin, sulfonylureas, glycemic control, HbA1c, fasting blood glucose, hypoglycemia, insulin-naive patients, insulin dose adjustment
MeSH terms: Insulin Glargine, Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Sulfonylurea Compounds, Weight Gain, Insulin, Long-Acting

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Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes

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