Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes
Open accessAbstract
OBJECTIVE—Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1–degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study. RESEARCH DESIGN AND METHODS—A total of 93 patients (61 men and 32 women), aged 64 ± 9 years (means ± SD) and with BMI 27.3 ± 2.7 kg/m2, entered the study. Fasting blood glucose was 8.5 ± 1.5 mmol/l, and HbA1c was 7.4 ± 0.7%. Before and after treatment with NVP DPP728 at 100 mg × 3 (n = 31) or 150 mg × 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal). RESULTS—Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA1c was reduced to 6.9 ± 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups. CONCLUSIONS—We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.
“Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.[35][36][37]”
From Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema (2008) · cites this paper as [35]
Studies report an increased incidence of nasopharyngitis in subjects randomly assigned to DPPIV inhibitor.
“However, studies report an increased incidence of nasopharyngitis in subjects randomly assigned to DPPIV inhibitor 35,38,40 ; in 1 study, 1 of 175 sitagliptin-treated subjects was hospitalized for angioedema.41”
From Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema (2008) · cites this paper as [35]
Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.
“Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.[35][36][37][38][39]”
From Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema (2008) · cites this paper as [35]
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- Authors
- Ahrén, B., Simonsson, E., Larsson, H., Landin-Olsson, M., Torgeirsson, H., Jansson, P.-A., Sandqvist, M., Båvenholm, P., Efendic, S., Eriksson, J. W., Dickinson, S., & Holmes, D.
- Affiliations
- Department of Medicine, Lund University, Malmö, Sweden
- Lund University (SE)
- Department of Medicine, Lund University, Lund, Sweden
- University of Gothenburg (SE)
- Department of Medicine, Göteborg University, Göteborg, Sweden
- Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden
- Umeå University (SE)
- Novartis (Switzerland) (CH)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2002-05-01
- Volume
- 25
- Issue
- 5
- Pages
- 869-875
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2146232529
- Semantic Scholar
- 08836146e8cd61a96643ff97a1516dbea54e3e63
- Cited by
- 421
- References
- 25
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 8 · 2015: 4 · 2014: 14 · 2013: 15 · 2012: 15
- FWCI
- 26.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- DPP-4 inhibitors, type 2 diabetes, glycemic control, HbA1c, fasting blood glucose, insulin, glucagon-like peptide-1, oral antidiabetic drugs, diet-controlled diabetes, insulin resistance, weight gain, adverse events
- MeSH terms
- Adult, Aged, Aged, 80 and over, Blood Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Insulin, Male, Middle Aged, Nitriles, Pyrrolidines, Time Factors, Treatment Outcome, Dipeptidyl Peptidase 4
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