Sitagliptin and metformin combination therapy for the treatment of Type 2 diabetes

References

• Smyth S, Heron A. Diabetes and obesity: the twin epidemics. Nat. Med.12, 75–80 (2006).
   PubMed Web of Science ®Google Scholar
• Gallwitz B. Therapies for the treatment of Type 2 diabetes mellitus based on incretin action. Minerva Endocrinol.31, 133–147 (2006).
   PubMedGoogle Scholar
• Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in Type 2 diabetes. Lancet368, 1696–1705 (2006).
   PubMed Web of Science ®Google Scholar
• Kahn SE, Haffner SM, Heise MA et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med.355, 2427–2443 (2006).
   PubMed Web of Science ®Google Scholar
• UKPDS Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with Type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet352, 854–865 (1998).
   PubMed Web of Science ®Google Scholar
• Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of Type 2 diabetes mellitus. Diabetes58, 773–795 (2009).
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Current management strategies for coexisting diabetes mellitus and obesity. Drugs63, 1165–1184 (2003).
   PubMed Web of Science ®Google Scholar
• Prentki M, Nolan CJ. Islet β cell failure in Type 2 diabetes. J. Clin. Invest.116, 1802–1812 (2006).
   PubMed Web of Science ®Google Scholar
• Lindeman RD, Romero LJ, Hundley R et al. Prevalences of Type 2 diabetes, the insulin resistance syndrome, and coronary heart disease in an elderly, biethnic population. Diabetes Care21, 959–966 (1998).
   PubMed Web of Science ®Google Scholar
• Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture (2005). Diabetologia49, 253–260 (2006).
   PubMed Web of Science ®Google Scholar
• Taylor R, Magnusson I, Rothman DL et al. Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects. J. Clin. Invest.97, 126–132 (1996).
   PubMed Web of Science ®Google Scholar
• Stumvoll M, Haring HU, Matthaei S. Metformin. Endocr. Res.32, 39–57 (2007).
   PubMed Web of Science ®Google Scholar
• Bailey CJ, Turner RC. Metformin. N. Engl. J. Med.334, 574–579 (1996).
   PubMed Web of Science ®Google Scholar
• Ahren B. Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin. Emerg. Drugs13, 593–607 (2008).
   PubMed Web of Science ®Google Scholar
• Dhillon S. Sitagliptin: a review of its use in the management of Type 2 diabetes mellitus. Drugs70, 489–512 (2010).
   PubMed Web of Science ®Google Scholar
• Gallwitz B. Review of sitagliptin phosphate: a novel treatment for Type 2 diabetes. Vasc. Health Risk Manag.3, 203–210 (2007).
   PubMedGoogle Scholar
• Gallwitz B. Sitagliptin: profile of a novel DPP-4 inhibitor for the treatment of Type 2 diabetes (update). Drugs Today (Barc.)43, 801–814 (2007).
   PubMed Web of Science ®Google Scholar
• Mu J, Woods J, Zhou YP et al. Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic β-cell mass and function in a rodent model of Type 2 diabetes. Diabetes55, 1695–1704 (2006).
   PubMed Web of Science ®Google Scholar
• Mu J, Petrov A, Eiermann GJ et al. Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of Type 2 diabetes. Eur. J. Pharmacol.623, 148–154 (2009).
   PubMed Web of Science ®Google Scholar
• Scheen AJ, Radermecker RP. Addition of incretin therapy to metformin in Type 2 diabetes. Lancet375, 1410–1412 (2010).
   PubMed Web of Science ®Google Scholar
• Scheen AJ. Pharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin. Expert Opin. Drug Metab. Toxicol.6, 1265–1276 (2010).
   PubMed Web of Science ®Google Scholar
• Salpeter S, Greyber E, Pasternak G, Salpeter E. Risk of fatal and nonfatal lactic acidosis with metformin use in Type 2 diabetes mellitus. Cochrane Database Syst. Rev.CD002967 (2006).
   Google Scholar
• Marchetti P, Del Guerra S, Marselli L et al. Pancreatic islets from Type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J. Clin. Endocrinol. Metab.89, 5535–5541 (2004).
   PubMed Web of Science ®Google Scholar
• Matthaei S, Bierwirth R, Fritsche A et al. Medical antihyperglycaemic treatment of Type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp. Clin. Endocrinol. Diabetes117, 522–557 (2009).
   PubMed Web of Science ®Google Scholar
• Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycaemia 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. Diabetologia52, 17–30 (2009).
   PubMed Web of Science ®Google Scholar
• Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of Type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med.346, 393–403 (2002).
   PubMed Web of Science ®Google Scholar
• Desilets AR, Dhakal-Karki S, Dunican KC. Role of metformin for weight management in patients without Type 2 diabetes. Ann. Pharmacother.42, 817–826 (2008).
   PubMed Web of Science ®Google Scholar
• Bergman AJ, Stevens C, Zhou Y et al. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin. Ther.28, 55–72 (2006).
   PubMed Web of Science ®Google Scholar
• Herman GA, Bergman A, Stevens C et al. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with Type 2 diabetes. J. Clin. Endocrinol. Metab.91, 4612–4619 (2006).
   PubMed Web of Science ®Google Scholar
• Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with Type 2 diabetes inadequately controlled with metformin alone. Diabetes Care29, 2638–2643 (2006).
   PubMed Web of Science ®Google Scholar
• Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with Type 2 diabetes. Diabetes Care29, 2632–2637 (2006).
   PubMed Web of Science ®Google Scholar
• 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.48, 141–151 (2005).
   PubMed Web of Science ®Google Scholar
• Miller S, St Onge EL. Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes. Ann. Pharmacother.40, 1336–1343 (2006).
   PubMed Web of Science ®Google Scholar
• Thornberry NA, Weber AE. Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes. Curr. Top. Med. Chem.7, 557–568 (2007).
   PubMed Web of Science ®Google Scholar
• Aschner P, Katzeff HL, Guo H et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with Type 2 diabetes. Diabetes Obes. Metab.12, 252–261 (2010).
   PubMed Web of Science ®Google Scholar
• Chan JC, Scott R, Arjona Ferreira JC et al. Safety and efficacy of sitagliptin in patients with Type 2 diabetes and chronic renal insufficiency. Diabetes Obes. Metab.10, 545–555 (2008).
   PubMed Web of Science ®Google Scholar
• Chu XY, Bleasby K, Yabut J et al. Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J. Pharmacol. Exp. Ther.321, 673–683 (2007).
   PubMed Web of Science ®Google Scholar
• Vincent SH, Reed JR, Bergman AJ et al. Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans. Drug Metab. Dispos.35, 533–538 (2007).
   PubMed Web of Science ®Google Scholar
• Hanefeld M, Herman GA, Wu M, Mickel C, Sanchez M, Stein PP. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with Type 2 diabetes. Curr. Med. Res. Opin.23, 1329–1339 (2007).
   PubMed Web of Science ®Google Scholar
• 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.9, 733–745 (2007).
   PubMed Web of Science ®Google Scholar
• Mohan V, Yang W, Son HY et al. Efficacy and safety of sitagliptin in the treatment of patients with Type 2 diabetes in China, India, and Korea. Diabetes Res. Clin. Pract.83, 106–116 (2009).
   PubMed Web of Science ®Google Scholar
• Nonaka K, Tsubouchi H, Okuyama K et al. Effects of once-daily sitagliptin on 24-h glucose control following 4 weeks of treatment in Japanese patients with Type 2 diabetes mellitus. Horm. Metab. Res.41, 232–237 (2009).
   PubMed Web of Science ®Google Scholar
• Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with Type 2 diabetes mellitus. Diabetologia49, 2564–2571 (2006).
   PubMed Web of Science ®Google Scholar
• Scott R, Wu M, Sanchez M, Stein P. Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with Type 2 diabetes. Int. J. Clin. Pract.61, 171–180 (2007).
   PubMed Web of Science ®Google Scholar
• Nonaka K, Kakikawa T, Sato A et al. Efficacy and safety of sitagliptin monotherapy in Japanese patients with Type 2 diabetes. Diabetes Res. Clin. Pract.79, 291–298 (2008).
   PubMed Web of Science ®Google Scholar
• Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with Type 2 diabetes: a review of recent clinical trials. Curr. Med. Res. Opin.24, 489–496 (2008).
   PubMed Web of Science ®Google Scholar
• Riche DM, East HE, Riche KD. Impact of sitagliptin on markers of β-cell function: a meta-analysis. Am. J. Med. Sci.337, 321–328 (2009).
   PubMed Web of Science ®Google Scholar
• Nauck MA, Homberger E, Siegel EG et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J. Clin. Endocrinol. Metab.63, 492–498 (1986).
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with Type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin. Ther.28, 1556–1568 (2006).
   PubMed Web of Science ®Google Scholar
• 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 Obes. Metab.12, 442–451 (2010).
   PubMed Web of Science ®Google Scholar
• Mannucci E, Ognibene A, Cremasco F et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care24, 489–494 (2001).
   PubMed Web of Science ®Google Scholar
• Mannucci E, Tesi F, Bardini G et al. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes. Diabetes Nutr. Metab.17, 336–342 (2004).
   PubMedGoogle Scholar
• Yasuda N, Inoue T, Nagakura T et al. Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Biochem. Biophys. Res. Commun.298, 779–784 (2002).
   PubMed Web of Science ®Google Scholar
• Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with Type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes. Metab.9, 194–205 (2007).
   PubMed Web of Science ®Google Scholar
• Migoya EM, Bergeron R, Miller JL et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin. Pharmacol. Ther.88, 801–808 (2010).
   PubMed Web of Science ®Google Scholar
• Maida A, Lamont BJ, Cao X, Drucker DJ. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice. Diabetologia54, 339–349 (2011).
   PubMed Web of Science ®Google Scholar
• Cho YM, Kieffer TJ. New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser. Diabetologia54, 219–222 (2011).
   PubMed Web of Science ®Google Scholar
• Knop FK. Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in Type 2 diabetes? Am. J. Physiol. Endocrinol. Metab.299, E10–E13 (2010).
   Google Scholar
• Yao X, Chen L, McIntyre MS et al. Biguanide antidiabetic agents increase fecal bile acids via inhibition of apical sodium-dependent bile acid transporter. Diabetes59 (2011) (Abstract 611-P).
   Google Scholar
• Yasuda N, Inoue T, Nagakura T et al. Metformin causes reduction of food intake and body weight gain and improvement of glucose intolerance in combination with dipeptidyl peptidase IV inhibitor in Zucker fa/fa rats. J. Pharmacol. Exp. Ther.310, 614–619 (2004).
   PubMed Web of Science ®Google Scholar
• Florentin M, Liberopoulos EN, Mikhailidis DP, Elisaf MS. Sitagliptin in clinical practice: a new approach in the treatment of Type 2 diabetes. Expert Opin. Pharmacother.9, 1705–1720 (2008).
   PubMed Web of Science ®Google Scholar
• Green J, Feinglos M. New combination treatments in the management of diabetes: focus on sitagliptin-metformin. Vasc. Health Risk Manag.4, 743–751 (2008).
   PubMedGoogle Scholar
• Reynolds JK, Neumiller JJ, Campbell RK. Janumet: a combination product suitable for use in patients with Type 2 diabetes. Expert Opin. Investig. Drugs17, 1559–1565 (2008).
   PubMed Web of Science ®Google Scholar
• Herman GA, Bergman A, Yi B, Kipnes M. Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with Type 2 diabetes. Curr. Med. Res. Opin.22, 1939–1947 (2006).
   PubMed Web of Science ®Google Scholar
• Bergman AJ, Cote J, Yi B et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care30, 1862–1864 (2007).
   PubMed Web of Science ®Google Scholar
• Williams-Herman D, Engel SS, Round E et al. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with Type 2 diabetes. BMC Endocr. Disord.10, 7 (2010).
   PubMed Web of Science ®Google Scholar
• Migoya EM, Stevens CH, Bergman AJ et al. Effect of moderate hepatic insufficiency on the pharmacokinetics of sitagliptin. Can. J. Clin. Pharmacol.16, e165–e170 (2009).
   PubMedGoogle Scholar
• Ahren B. Novel combination treatment of Type 2 diabetes DPP-4 inhibition + metformin. Vasc. Health Risk Manag.4, 383–394 (2008).
   PubMedGoogle Scholar
• Gallwitz B. Sitagliptin with metformin. profile of a combination for the treatment of Type 2 diabetes. Drugs Today (Barc.)43, 681–689 (2007).
   PubMed Web of Science ®Google Scholar
• Raz I, Chen Y, Wu M et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with Type 2 diabetes. Curr. Med. Res. Opin.24, 537–550 (2008).
   PubMed Web of Science ®Google Scholar
• Scott R, Loeys T, Davies MJ, Engel SS. Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with Type 2 diabetes. Diabetes Obes. Metab.10, 959–969 (2008).
   PubMed Web of Science ®Google Scholar
• Seck T, Nauck M, Sheng D et al. Safety and efficacy of treatment with sitagliptin or glipizide in patients with Type 2 diabetes inadequately controlled on metformin: a 2-year study. Int. J. Clin. Pract.64, 562–576 (2010).
   PubMed Web of Science ®Google Scholar
• Arechavaleta R, Seck T, Chen Y et al. Efficacy and safety of treatment with sitagliptin or glimepiride in patients with Type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial. Diabetes Obes. Metab.13, 160–168 (2011).
   PubMed Web of Science ®Google Scholar
• Bergenstal RM, Wysham C, Macconell L et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of Type 2 diabetes (DURATION-2): a randomised trial. Lancet376, 431–439 (2010).
   PubMed Web of Science ®Google Scholar
• Pratley RE, Nauck M, Bailey T et al. Liraglutide versus sitagliptin for patients with Type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet375, 1447–1456 (2010).
   PubMed Web of Science ®Google Scholar
• Fakhoury WK, Lereun C, Wright D. A meta-analysis of placebo-controlled clinical trials assessing the efficacy and safety of incretin-based medications in patients with Type 2 diabetes. Pharmacology86, 44–57 (2010).
   PubMed Web of Science ®Google Scholar
• Fonseca V, Desouza C, Khan AN. Adding subcutaneous liraglutide to metformin reduces HbA1c more than adding oral sitagliptin in patients whose Type 2 diabetes is poorly controlled with metformin alone. Evid. Based Med.15, 115–116 (2010).
   PubMedGoogle Scholar
• Schwarz B, Gouveia M, Chen J et al. Cost–effectiveness of sitagliptin-based treatment regimens in European patients with Type 2 diabetes and haemoglobin A1c above target on metformin monotherapy. Diabetes Obes. Metab.10(Suppl. 1), 43–55 (2008).
   PubMed Web of Science ®Google Scholar
• Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with Type 2 diabetes. Diabetes Care30, 1979–1987 (2007).
   PubMed Web of Science ®Google Scholar
• 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. Res. Opin.25, 569–583 (2009).
   PubMed Web of Science ®Google Scholar
• Ahren B, Schweizer A, Dejager S et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with Type 2 diabetes. J. Clin. Endocrinol. Metab.94, 1236–1243 (2009).
   PubMed Web of Science ®Google Scholar
• Goke B, Gallwitz B, Eriksson J, Hellqvist A, Gause-Nilsson I. Saxagliptin is non-inferior to glipizide in patients with Type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial. Int. J. Clin. Pract.64, 1619–1631 (2010).
   PubMed Web of Science ®Google Scholar
• Nissen SE. Setting the RECORD straight. JAMA303, 1194–1195 (2010).
   PubMed Web of Science ®Google Scholar
• Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can. J. Diabetes32, S01–S201 (2008).
   Web of Science ®Google Scholar
• AACE Diabetes Mellitus Clinical Practice Guidelines Task Force: American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr. Pract.13, 1–66 (2007).
   PubMedGoogle Scholar
• Reasner CA, Olansky L, Seck TL et al. Initial therapy with the fixed-dose combination (FDC) of sitagliptin and metformin (JANUMET™) in patients with Type 2 diabetes mellitus (T2DM) provides superior glycemic control and A1C goal attainment with lower rates of abdominal pain and diarrhea vs. metformin alone. Diabetes58, 610 (2009).
   Google Scholar
• Gallwitz B. Therapies for the treatment of Type 2 diabetes mellitus based on incretin action. Minerva Endocrinol.31, 133–147 (2006).
   PubMedGoogle Scholar
• Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH. The role of CD26/dipeptidyl peptidase IV in cancer. Front. Biosci.13, 1634–1645 (2008).
   PubMed Web of Science ®Google Scholar
• Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Increased incidence of pancreatitis and cancer among patients given glucagon like peptide-1 based therapy. Gastroenterology DOI: 10.1053/j.gastro.2011.02.018 (2011) (Epub ahead of print).
   PubMedGoogle Scholar
• Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in Type 2 diabetes. Diabetologia52, 1766–1777 (2009).
   PubMed Web of Science ®Google Scholar
• Vilsboll T, Rosenstock J, Yki-Jarvinen H et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with Type 2 diabetes. Diabetes Obes. Metab.12, 167–177 (2010).
   PubMed Web of Science ®Google Scholar