Effects of Sitaglipin Combined with Metformin for Type 2 Diabetes Mellitus: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

LI Ji ,  SUN Jiazhong , LI Guangsen , DAI Jing

Department of Endocrinology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China;

Corresponding author：

SUN Jiazhong, Email: sjz300@163.com

Keywords：

Type 2 diabetes mellitus; Sitgliptin; Metformin; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20130149

Video：

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Objective 　To assess the effects and safety of sitagliptin combined with metformin in treating type 2 diabetes mellitus.
Methods 　The Cochrane Library, PubMed, EMbase, CNKI, WanFang Data, VIP and CBM were searched to collect the randomized controlled trials (RCTs) on sitagliptin combined with metformin in treating Type 2 diabetes mellitus (T2DM) from inception to November, 2012. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.1 software.
Results 　7 RCTs involving 2 917 patients were included. The results of meta-analysis showed that, compared with metformin alone, sitagliptin combined with metformin effectively improved HbA1c levels (WMD= –0.62%, 95%CI –0.76 to –0.47, P lt;0.000 1) and fasting plasma glucose levels (WMD= –0.7 mmol/L, 95%CI –1.03 to –0.37, P lt;0.000 01), and increased insulin sensitivity and β-cell function. But there was no significant difference between the two groups in the incidences of gastrointestinal reactions and hypoglycemia.
Conclusion 　Compared with using metformin alone, sitagliptin combined with metformin can improve glycemic control, enhance insulin sensitivity and better β-cell function more effectively and both have a similar effect on weight lose, but there is no significant difference he incidences of gastrointestinal reactions and hypoglycemia. The above conclusion should be verified by more large-scale high-quality studies in future due to the limitations of the methodological quality and sample size of the included studies.

Citation： LI Ji,SUN Jiazhong,LI Guangsen,DAI Jing. Effects of Sitaglipin Combined with Metformin for Type 2 Diabetes Mellitus: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2013, 13(7): 836-843. doi: 10.7507/1672-2531.20130149 Copy

1.	Nathan DM, Buse JB, Davidson MB, et al. 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 forthe Study of Diabetes. Diabetes Care, 2009, 32(1): 193-203.
2.	潘长玉, 金文胜. 2型糖尿病流行病学. 中华内分泌杂志, 2005, 21(5)增录5: 1-5.
3.	迟家敏. 实用糖尿病学. 第3版, 北京: 人民卫生出版社, 2009: 1-5.
4.	Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35):prospective observational study. BMJ, 2000, 321(4): 405-412.
5.	The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med, 1993, 329(5): 977-986.
6.	Setter SM, lltz JL, Thams J, et al. Metformin hydrochloride in the treatment of type 2 diabetes mellitus:a clinical review with a focus on dual therapy. ClinTher, 2003, 25(2): 2991-3026.
7.	Rosenstock J, Rood J, Cobitz A, et al. Initial treatment with rosiglitazone/metform in fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes. Diabetes Obes Metab, 2006, 8(6): 650-660.
8.	Garber AJ, Donovan DS, Dandona P, et al. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. J Clin Endocrinol Metab, 2003, 88(3): 3598-3604.
9.	Deeks ED, Scott LJ. Pioglitazone/metformin. Drugs, 2006, 66(4): 1863-1877.
10.	Hundal RS, Inzucchi SE. Metformin:new understandings,new uses. Drugs, 2003, 63(8): 1879-1894.
11.	Mannucci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptins levels in obese nondiabetic subjects. Diabetes Care, 2001, 24(3): 489-494.
12.	Hinke SA, Kuhn-Wache K, Hoffmann T, et al. Metformin effects on dipeptidylpeptidase Ⅳ degradation of glucagon-like peptide-1. Biochem Biophys Res Commun, 2002, 291(7): 1302-1308.
13.	Lenhard JM, Croom DK, Minnnick DT. Reduced serum dipeptidyl peptidase-Ⅳ after metformin and pioglitazone treatments. Biochem Biophy Res Commun, 2004, 324(3): 92-97.
14.	Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA, 2004, 291(5): 335-342.
15.	Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multipletherapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA, 1999, 281(6): 2005-2012.
16.	Liebl A, Mata M, Eschwege E. Evaluation of risk factors for development of complications in type II diabetes in Europe. Diabetologia, 2002, 45(4): 23-28.
17.	Kim D, Wang L, Beconi M, et al. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl) butan-2-amine:a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem, 2005, 48(6): 141-151.
18.	Druker DJ, Nauck MA. GLP-1R agonists(incretin mimetics) and DPP-4 inhibitors (incretin enhancers) forthe treatment of type 2 diabetes. Lancet, 2006, 368(3): 1696-1705.
19.	Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes:a 54-week study. Curr Med ResOpin, 2009, 25(3): 569-583.
20.	Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care, 2006, 29(12): 2632-2637.
21.	Matthews DR, Hosker JP, Rudenski AS, et al. meostasis model assessment: insulin esistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7): 412-419.
22.	Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studiesin subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 2000, 23(1): 57-63.
23.	Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 2010, 23(12): 442-451.
24.	Olansky L, Reasner C, Seck TL. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin mon-otherapy due to a low rate of addition of antihyperglycaemic agents. Diabetes, Obesity and Metabolism, 2011, 13(9): 841-849.
25.	Reasner C, Olansky L, Seck TL. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism, 2011, 13(2): 644-652.
26.	Williams-Herman D, Xu L, Teng R, et al. Effect of initial combination therapy with sitagliptin and metformin on β-cell function in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 2012, 14(7): 67-76.
27.	赵晓航. 西格列汀联合二甲双胍治疗2型糖尿病的疗效观察. 中外医疗, 2012, 31(22): 77, 79.
28.	纪万军, 于立芹, 滕川. 西格列汀联合二甲双胍2型糖尿病的临床研究. 中国医药指南, 2012, 10(18): 222-223.
29.	黄宾协. 西格列汀联合二甲双胍治疗初发糖尿病的临床观察. 中国医疗前沿, 2011, 6(6): 58.

1. Nathan DM, Buse JB, Davidson MB, et al. 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 forthe Study of Diabetes. Diabetes Care, 2009, 32(1): 193-203.
2. 潘长玉, 金文胜. 2型糖尿病流行病学. 中华内分泌杂志, 2005, 21(5)增录5: 1-5.
3. 迟家敏. 实用糖尿病学. 第3版, 北京: 人民卫生出版社, 2009: 1-5.
4. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35):prospective observational study. BMJ, 2000, 321(4): 405-412.
5. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med, 1993, 329(5): 977-986.
6. Setter SM, lltz JL, Thams J, et al. Metformin hydrochloride in the treatment of type 2 diabetes mellitus:a clinical review with a focus on dual therapy. ClinTher, 2003, 25(2): 2991-3026.
7. Rosenstock J, Rood J, Cobitz A, et al. Initial treatment with rosiglitazone/metform in fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes. Diabetes Obes Metab, 2006, 8(6): 650-660.
8. Garber AJ, Donovan DS, Dandona P, et al. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. J Clin Endocrinol Metab, 2003, 88(3): 3598-3604.
9. Deeks ED, Scott LJ. Pioglitazone/metformin. Drugs, 2006, 66(4): 1863-1877.
10. Hundal RS, Inzucchi SE. Metformin:new understandings,new uses. Drugs, 2003, 63(8): 1879-1894.
11. Mannucci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptins levels in obese nondiabetic subjects. Diabetes Care, 2001, 24(3): 489-494.
12. Hinke SA, Kuhn-Wache K, Hoffmann T, et al. Metformin effects on dipeptidylpeptidase Ⅳ degradation of glucagon-like peptide-1. Biochem Biophys Res Commun, 2002, 291(7): 1302-1308.
13. Lenhard JM, Croom DK, Minnnick DT. Reduced serum dipeptidyl peptidase-Ⅳ after metformin and pioglitazone treatments. Biochem Biophy Res Commun, 2004, 324(3): 92-97.
14. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA, 2004, 291(5): 335-342.
15. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multipletherapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA, 1999, 281(6): 2005-2012.
16. Liebl A, Mata M, Eschwege E. Evaluation of risk factors for development of complications in type II diabetes in Europe. Diabetologia, 2002, 45(4): 23-28.
17. Kim D, Wang L, Beconi M, et al. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl) butan-2-amine:a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem, 2005, 48(6): 141-151.
18. Druker DJ, Nauck MA. GLP-1R agonists(incretin mimetics) and DPP-4 inhibitors (incretin enhancers) forthe treatment of type 2 diabetes. Lancet, 2006, 368(3): 1696-1705.
19. Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes:a 54-week study. Curr Med ResOpin, 2009, 25(3): 569-583.
20. Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care, 2006, 29(12): 2632-2637.
21. Matthews DR, Hosker JP, Rudenski AS, et al. meostasis model assessment: insulin esistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7): 412-419.
22. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studiesin subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 2000, 23(1): 57-63.
23. Williams-Herman D, Johnson J, Teng R, et al. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 2010, 23(12): 442-451.
24. Olansky L, Reasner C, Seck TL. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycaemic control versus metformin mon-otherapy due to a low rate of addition of antihyperglycaemic agents. Diabetes, Obesity and Metabolism, 2011, 13(9): 841-849.
25. Reasner C, Olansky L, Seck TL. The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus. Diabetes, Obesity and Metabolism, 2011, 13(2): 644-652.
26. Williams-Herman D, Xu L, Teng R, et al. Effect of initial combination therapy with sitagliptin and metformin on β-cell function in patients with type 2 diabetes. Diabetes, Obesity and Metabolism, 2012, 14(7): 67-76.
27. 赵晓航. 西格列汀联合二甲双胍治疗2型糖尿病的疗效观察. 中外医疗, 2012, 31(22): 77, 79.
28. 纪万军, 于立芹, 滕川. 西格列汀联合二甲双胍2型糖尿病的临床研究. 中国医药指南, 2012, 10(18): 222-223.
29. 黄宾协. 西格列汀联合二甲双胍治疗初发糖尿病的临床观察. 中国医疗前沿, 2011, 6(6): 58.

Chinese Journal of Evidence-Based Medicine

Effects of Sitaglipin Combined with Metformin for Type 2 Diabetes Mellitus: A Systematic Review

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