Efficacy and Safety of Switching from Basal Insulin to Sitagliptin in Japanese Type 2 Diabetes Patients

Abstract

Basal-supported oral therapy (BOT) is often used to treat poorly controlled type 2 diabetes. However, patients sometimes experience nocturnal and early morning hypoglycemia. Thus, maintaining targeted glycemic control by BOT is limited in some patients. We assessed the efficacy and safety of replacing basal insulin by sitagliptin therapy in Japanese type 2 diabetes patients on BOT. Forty-nine subjects were sequentially recruited for the 52-week, prospective, single arm study. Patients on BOT therapy were switched from basal insulin to sitagliptin. The primary endpoint was change in HbA1c in 52 weeks. The secondary endpoints were dropout rate, changes in body weight, frequency of hypoglycemia, and relationship between change in HbA1c and insulin secretion capacity evaluated by glucagon loading test. The average dose of basal insulin was 15.0±8.4 units. Sixteen subjects (31.3%) were dropped because replacement by sitagliptin was less effective for glycemic control. In these subjects, diabetes duration was longer, FPG and HbA1c at baseline were higher, and insulin secretion capacity was lower. Change in HbA1c in 52 weeks was  − 4 mmol/mol (95% CI  − 5 to  − 4 mmol/mol) (p<0.05). Change in body weight was  − 0.71 kg (95% CI  − 1.42 to  − 0.004 kg) (p<0.05). Frequency of hypoglycemia was decreased from 1.21±1.05 to 0.06±0.24 times/month. HbA1c level was improved if C-peptide index (CPI) was over 1.19. In conclusion, basal insulin in BOT can be replaced by sitagliptin with a decrease in HbA1c level and frequency of hypoglycemia in cases where insulin secretion capacity was sufficiently preserved.

Key words

sitagliptin - basal insulin - insulin secretion capacity

• References

• 1 Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. American Diabetes Association; European Association for Study of Diabetes . Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203
• 2 Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. American Diabetes Association; European Association for Study of Diabetes . Medical management of hyperglycemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2009; 52: 17-30
• 3 Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 2000; 23: 644-649
• 4 Plank J, Bodenlenz M, Sinner F, Magnes C, Görzer E, Regittnig W, Endahl LA, Draeger E, Zdravkovic M, Pieber TR. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care 2005; 28: 1107-1112
• 5 Swinnen SG, Simon AC, Holleman F, Hoekstra JB, Devries JH. Insulin detemir versus insulin glargine for type 2 diabetes mellitus. Cochrane Database Syst Rev 2011; 6 CD006383
• 6 Blicklé JF, Hancu N, Piletic M, Profozic V, Shestakova M, Dain MP, Jacqueminet S, Grimaldi A. Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7–8% A1c levels. The TULIP study. Diabetes Obes Metab 2009; 11: 379-386
• 7 Schreiber SA, Ferlinz K, Haak T. The long-term efficacy of insulin glargine plus oral antidiabetic agents in a 32-month observational study of everyday clinical practice. Diabetes Technol Ther 2008; 10: 121-127
• 8 Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire JL, Keenan JF, Paul SK. 4-T Study Group . Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009; 361: 1736-1747
• 9 Pfohl M, Dippel FW, Kostev K, Fuchs S, Kotowa W. Different persistence on initial basal supported oral therapy in Type 2 diabetics is associated with unequal distributions of insulin treatment regimens under real-life conditions in Germany. Int J Clin Pharmacol Ther 2010; 48: 761-766
• 10 Kadowaki T. Analysis of ALOHA (add-on Lantus^® to OHA) study: Basal supported oral therapy (BOT) with insulin glargine resulted in reduction of HbA1c, FPG and PPG with nearly 2% incidence of adverse drug reactions. Dubai: World Diabetes Congress; 2011
• 11 Seino Y, Fukushima M, Yabe D. GIP and GLP-1, two incretin hormones: Similarities and differences. J Diabetes Invest 2010; 1: 8-23
• 12 Tajima N, Kadowaki T, Odawara M, Nishi M, Taniguchi T, Arjona Ferreira JC. Addition of sitagliptin to ongoing glimepiride therapy in Japanese patients with type 2 diabetes over 52 weeks leads to improved glycemic control. Diabetol Int 2011; 2: 32-44
• 13 Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007; 9: 733-745
• 14 Harashima SI, Ogura M, Tanaka D, Fukushima T, Wang Y, Koizumi T, Aono M, Murata Y, Seike M, Inagaki N. Sitagliptin add-on to low dosage sulfonylureas: efficacy and safety of combination therapy on glycemic control and insulin secretion capacity in type 2 diabetes. Int J Clin Prac 2012; 66: 465-476
• 15 Kubota A, Matsuba I, Saito T, Nabe K, Seino Y. Secretory units of islets in transplantation index is a useful clinical marker to evaluate the efficacy of sitagliptin in treatment of type 2 diabetes mellitus. J Diabetes Invest 2011; 5: 377-380
• 16 Fukushima M, Usami M, Ikeda M, Nakai Y, Taniguchi A, Matsuura T, Suzuki H, Kurose T, Yamada Y, Seino Y. Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism 2004; 53: 831-835
• 17 Fukushima M, Suzuki H, Seino Y. Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes. Diabetes Res Clin Pract 2004; 66: S37-S47
• 18 Abdul-Ghani MA, Matsuda M, Jani R, Jenkinson CP, Coletta DK, Kaku K, DeFronzo RA. The relationship between fasting hyperglycemia and insulin secretion subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab 2008; 295: E401-E406
• 19 Funakoshi S, Fujimoto S, Hamasaki A, Fujiwara H, Fujita Y, Ikeda K, Hamamoto Y, Hosokawa M, Seino Y, Inagaki N. Analysis of factors influencing pancreatic beta-cell function in Japanese patients with type 2 diabetes: Association with body mass index and duration of diabetic exposure. Diabetes Res Clin Pract 2008; 82: 353-358
• 20 Yamada Y, Fukuda K, Fujimoto S, Hosokawa M, Tsukiyama K, Nagashima K, Fukushima M, Suzuki H, Toyoda K, Sassa M, Funakoshi S, Inagaki N, Taniguchi A, Sato TS, Matsumoto S, Tanaka K, Seino Y. SUIT, secretory units of islets in transplantation: An index for therapeutic management of islet transplanted patients and its application to type 2 diabetes. Diabetes Res Clin Pract 2006; 74: 222-226
• 21 Esposito K, Cozzolino D, Bellastella G, Maiorino MI, Chiodini P, Ceriello A, Giugliano D. Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes Metab 2011; 13: 594-603
• 22 Gallwitz B, Häring HU. Future perspectives for insulinotropic agents in the treatment of type 2 diabetes-DPP-4 inhibitors and sulphonylureas. Diabetes Obes Metab 2010; 12: 1-11
• 23 Zhang CL, Katoh M, Shibasaki T, Minami K, Sunaga Y, Takahashi T, Yokoi N, Iwasaki M, Miki T, Seino S. The cAMP sensor Rpac2 is a direct target of antidiabetic sulfonylurea drugs. Science 2009; 25: 607-610
• 24 Arai K, Matoba K, Hirao K, Matsuba I, Takai M, Takeda H, Kanamori A, Yamauchi M, Mori H, Terauchi Y. Present status of sulfonylurea treatment for type 2 diabetes in Japan: second report of a cross-sectional survey of 15 652 patients. Endocr J 2010; 57: 499-507
• 25 Welch S, Gebhart SS, Bergman RN, Phillips LS. Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. J Clin Endocrinol Metab 1990; 71: 1508-1518
• 26 Taniguchi A, Nakai Y, Fukushima M, Kawamura H, Imura H, Nagata I, Tokuyama K. Pathogenic factors responsible for glucose intolerance in patients with NIDDM. Diabetes 1992; 41: 1540-1546
• 27 Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011; 378: 182-197
• 28 DeFronzo RA. Current issues in the treatment of type 2 diabetes. Overview of newer agents: where treatment is going. Am J Med 2010; 123: S38-S48