Substitution of Chronic Insulin Therapy with Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-transporter-2 Inhibitors

Hideshi Okada*, Genzou Takemura, Kodai Suzuki, Nagisa Miyazaki, Eiji Kuroda, Yoko Ito, Toshihiko Chikaishi, Hiroaki Ushikoshi and Shinji Ogura

Corresponding Author

Hideshi Okada, MD, PhD

Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido Gifu 501-1194, Japan Tel. +81-58-230-6448 Fax: +81-58-230-6451 E-mail:


Hideshi Okada1,2*, Genzou Takemura2,3, Kodai Suzuki1, Nagisa Miyazaki2,4, Eiji Kuroda5, Yoko Ito4, Toshihiko Chikaishi4, Hiroaki Ushikoshi1 and Shinji Ogura1

1Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan

2Department of Internal Medicine, Chikaishi Clinic, Gifu, Japan

3Department of Internal Medicine, Asahi University, Hozumi 1851-1, Japan

4Department of Nephrology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan

5Department of Internal Medicine, Kaizu Medical Association Hospital, Kaizu, Japan

Corresponding Author

Hideshi Okada, MD, PhD

Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido Gifu 501-1194, Japan Tel. +81-58-230-6448 Fax: +81-58-230-6451 E-mail:

Article History

Received: June 30th, 2015 Accepted: July 10th, 2015 Published: July 13th, 2015

Cite this Article

Okada H, Takemura G, Suzuki K, et al. Substitution of chronic insulin therapy with dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors. Diabetes Res Open J. 2015; 1(3): 77-78. doi: 10.17140/DROJ-1-113


Ā© 2015 Okada H. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Insulin is a very useful and widely used treatment for diabetes. Temporary insulin therapy improves glucose toxicity due to improved Ī²-cell function of the pancreas. Upon achieving glycemic control, insulin treatment could be discontinued and substituted with oral hypoglycemic agents. Nevertheless, insulin therapy is associated with side effects such as hypoglycemia, allergic reactions, and angioneurotic edema. Over this past decade, there have been rapid advances in diabetes treatment, including the introduction of Dipeptidyl peptidase-4 (DPP-4) inhibitors and Sodium-glucose cotransporter-2 (SGLT2) inhibitors. We present here the case of a patient with type 2 diabetes who discontinued insulin therapy after more than 20 years by switching to oral hypoglycemic agents including a DPP-4 inhibitor and a SGLT2 inhibitor.

A 64-year-old man with type 2 diabetes was being treated with Lispro Mix 50 insulin twice daily. He was started on subcutaneous insulin 20 years ago. He also has hypertension and hyperlipidemia, and visits the home clinic once a month. He consulted the clinic because he strongly wanted to discontinue insulin therapy due to his work situation. At the time, he was taking Lispro Mix 50 insulin twice daily (morning: 10U, evening: 6U) and his HbA1c was 7.3%. His body weight was 47.0 kg, height was 160 cm, and body mass index was 18.4 kg/m2. His blood pressure was 118/68 mm Hg and his pulse rate was 72 beats per minute. After evaluation of his condition, insulin therapy was discontinued and oral therapy consisting of glimepiride 1 mg/day, teneligliptin 20 mg/day, and canagliflozin 100 mg/day was started. Serum C-peptide and HbA1c were 0.9 ng/ml and 7.3% respectively three months later.

In theory, the dose of insulin should be reduced gradually when oral hypoglycemic agents are added and insulin therapy is being discontinued. However, the patient demanded immediate discontinuation of insulin therapy. Since his insulin dose was relatively low, 0.3 U/kg, insulin was discontinued, and oral hypoglycemic agents were started at once after a comprehensive review of the risks and benefits of a sudden change in therapy.

Early introduction of short-term insulin therapy is more protective for the beta cells of pancreas than oral hypoglycemic therapy in patients with type 2 diabetes. Surprisingly, in the present case, although the duration of insulin therapy was over 20 years, serum C-peptide, an indicator of insulin secretion, was 0.9 ng/ml, which is not too low. This may be explained by the following: 1) glimepiride increases insulin release from the Ī²-cells of the pancreas, and 2) DPP-4 inhibitors increase incretin levels, which suppresses glucagon release, thereby increasing insulin secretion and decreases blood glucose levels.

SGLT2 inhibitors reduce hyperglycemia by increasing urinary glucose excretion independent of insulin secretion or action. In addition, it has been reported that SGLT2 inhibitors increase glucoseā€“dependent insulin secretion by improving Ī²-cell function of the pancreas.1

Based on the empiric evidence, DPP4 inhibitors and SGLT2 inhibitors are effective in patients who secrete less insulin after long-term insulin therapy since they do not have a direct effect on insulin secretion.




The patient has provided the informed written consent for this case to be published.

1. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose co-transporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014; 124(2): 499-508. doi: 10.1172/JCI72227


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