Diabetes Metab J.  2016 Dec;40(6):454-462. 10.4093/dmj.2016.40.6.454.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment

• Yang Y
• Shin JA
• Yang HK
• Lee SH
• Ko SH
• Ahn YB
• Yoon KH
• Cho JH

• KMID: 2362218
• DOI: http://doi.org/10.4093/dmj.2016.40.6.454

Abstract

BACKGROUND
There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin.
METHODS
In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT.
RESULTS
Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group.
CONCLUSION
Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Keyword

Basal insulin; Beta-cell; Diabetes mellitus, type 2; Recovery; Sulfonylurea

MeSH Terms

Diabetes Mellitus, Type 2*
Follow-Up Studies
Glucose Tolerance Test
Hemoglobin A, Glycosylated
Humans
Insulin*
Insulin, Long-Acting
Triglycerides
Weight Gain
Insulin
Insulin, Long-Acting
Triglycerides

Figure

• 

  Fig. 1 Changes in the glucose levels, body weight, and insulin and sulfonylurea (SU) doses over 6 months. Changes in the (A) glycosylated hemoglobin (HbA1c) levels, (B) body weight, and (C) injected insulin dose in the SU maintenance and SU reduction groups during the study period. (D) Dose reduction of SU in the SU reduction group. The data are presented as the mean±standard error.

• 

  Fig. 2 Changes in β-cell function and insulin resistance. Results of the 75-g oral glucose tolerance test. (A) The plasma glucose levels in the sulfonylurea (SU) maintenance and (B) SU reduction groups. (C) The plasma insulin levels in the SU maintenance and (D) SU reduction groups. The data are presented as the mean±standard error. aP<0.05 before and after insulin treatment.

Reference

1. DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988; 37:667–687.

2. Kim DJ, Lee MS, Kim KW, Lee MK. Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus. Metabolism. 2001; 50:590–593.

3. Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, Zimmet P, Son HY. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006; 368:1681–1688.

4. Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha BY, Lee KW, Son HY, Kang SK, Kim HS, Lee IK, Bonner-Weir S. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab. 2003; 88:2300–2308.

5. Turner LW, Nartey D, Stafford RS, Singh S, Alexander GC. Ambulatory treatment of type 2 diabetes in the U.S., 1997-2012. Diabetes Care. 2014; 37:985–992.

6. Jeon JY, Kim DJ, Ko SH, Kwon HS, Lim S, Choi SH, Kim CS, An JH, Kim NH, Won JC, Kim JH, Cha BY, Song KH. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Current status of glycemic control of patients with diabetes in Korea: the fifth Korea National Health and Nutrition Examination Survey. Diabetes Metab J. 2014; 38:197–203.

7. Suk JH, Lee CW, Son SP, Kim MC, Ahn JH, Lee KJ, Park JY, Shin SH, Kwon MJ, Kim SS, Kim BH, Lee SH, Park JH, Kim IJ. Relationship between Cardiovascular Disease and Brachial-Ankle Pulse Wave Velocity (baPWV) in Patients with Type 2 Diabetes (REBOUND) Study Group. Current status of prescription in type 2 diabetic patients from general hospitals in Busan. Diabetes Metab J. 2014; 38:230–239.

8. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015; 38:140–149.

9. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006; 355:2427–2443.

10. Qian L, Zhang S, Xu L, Peng Y. Endoplasmic reticulum stress in beta cells: latent mechanism of secondary sulfonylurea failure in type 2 diabetes? Med Hypotheses. 2008; 71:889–891.

11. Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY. Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab. 2005; 90:501–506.

12. Takahashi A, Nagashima K, Hamasaki A, Kuwamura N, Kawasaki Y, Ikeda H, Yamada Y, Inagaki N, Seino Y. Sulfonylurea and glinide reduce insulin content, functional expression of K(ATP) channels, and accelerate apoptotic beta-cell death in the chronic phase. Diabetes Res Clin Pract. 2007; 77:343–350.

13. Bolli GB, Lucidi P, Porcellati F, Fanelli CG. Pivotal role of timely basal insulin replacement after metformin failure in sustaining long-term blood glucose control at a target in type 2 diabetes. Diabetes Care. 2011; 34:Suppl 2. S220–S224.

14. Alvarsson M, Berntorp K, Fernqvist-Forbes E, Lager I, Steen L, Orn T, Grill V. Effects of insulin versus sulphonylurea on beta-cell secretion in recently diagnosed type 2 diabetes patients: a 6-year follow-up study. Rev Diabet Stud. 2010; 7:225–232.

15. Meneghini LF. Early insulin treatment in type 2 diabetes: what are the pros? Diabetes Care. 2009; 32:Suppl 2. S266–S269.

16. Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, Hu Y, Zhou Z, Yan X, Tian H, Ran X, Luo Z, Xian J, Yan L, Li F, Zeng L, Chen Y, Yang L, Yan S, Liu J, Li M, Fu Z, Cheng H. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008; 371:1753–1760.

17. Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. Diabetes Care. 2008; 31:1927–1932.

18. Pfutzner A, Lorra B, Abdollahnia MR, Kann PH, Mathieu D, Pehnert C, Oligschleger C, Kaiser M, Forst T. The switch from sulfonylurea to preprandial short-acting insulin analog substitution has an immediate and comprehensive beta-cell protective effect in patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2006; 8:375–384.

19. Alvarsson M, Sundkvist G, Lager I, Henricsson M, Berntorp K, Fernqvist-Forbes E, Steen L, Westermark G, Westermark P, Orn T, Grill V. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care. 2003; 26:2231–2237.

20. Castillo M, Scheen AJ, Paolisso G, Lefebvre PJ. The addition of glipizide to insulin therapy in type-II diabetic patients with secondary failure to sulfonylureas is useful only in the presence of a significant residual insulin secretion. Acta Endocrinol (Copenh). 1987; 116:364–372.

21. Del Prato S, Vigili de Kreutzenberg S, Riccio A, Maifreni L, Duner E, Lisato G, Iavicoli M, Tiengo A. Partial recovery of insulin secretion and action after combined insulin-sulfonylurea treatment in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral agents. Diabetologia. 1990; 33:688–695.

22. Wolffenbuttel BH, Weber RF, Weeks L, van Koetsveld PM, Verschoor L. Twice daily insulin therapy in patients with type 2 diabetes and secondary failure to sulphonylureas. Diabetes Res. 1990; 13:79–84.

23. Karam JH, Sanz N, Salamon E, Nolte MS. Selective unresponsiveness of pancreatic beta-cells to acute sulfonylurea stimulation during sulfonylurea therapy in NIDDM. Diabetes. 1986; 35:1314–1320.

24. Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994; 11:286–292.

25. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28:412–419.

26. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22:1462–1470.

27. Unger RH, Grundy S. Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: implications for the management of diabetes. Diabetologia. 1985; 28:119–121.

28. Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care. 1990; 13:610–630.

29. Garvey WT, Olefsky JM, Griffin J, Hamman RF, Kolterman OG. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes. 1985; 34:222–234.