Abstract
Diabetes is a global epidemic, associated with a high burden of complications and 4.6 million deaths annually worldwide. As a result of decreasing levels of physical activity and increasing rates of obesity, diabetes is shifting from a disease affecting the elderly to one that affects younger patients or even children. Thus, aggressive treatment and optimal control of risk factors is the key to improve outcomes in those patients. Accumulating evidence of the cardiovascular and lipid effects of glucose-lowering medications suggest that treatment efficacy in diabetes can be further improved. This review provides an overview of the lipid effects and cardiovascular disease risk of current anti-diabetic medications and highlights opportunities and challenges in clinical practice.
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Haffner SM, Lehto S, Ronnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.
Preis SR, Pencina MJ, Mann DM, et al. Early-adulthood cardiovascular disease risk factor profiles among individuals with and without diabetes in the Framingham Heart Study. Diabetes Care. 2013;36:1590–6.
Stamler J, Vaccaro O, Neaton JD, et al. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–44.
Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). Br Med J. 1998;316:823–8.
Tan CE, Chew LS, Chio LF, et al. Cardiovascular risk factors and LDL subfraction profile in Type 2 diabetes mellitus subjects with good glycaemic control. Diabetes Res Clin Pract. 2001;51:107–14.
Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5:150–9.
Chehade JM, Gladysz M, Mooradian AD. Dyslipidemia in type 2 diabetes: prevalence, pathophysiology, and management. Drugs. 2013;73:327–39. This article provides an excellent overview of the characteristics of diabetic dyslipidemia including pathophysiological aspects and clinical implications.
Buse JB, Tan MH, Prince MJ, et al. The effects of oral anti-hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes. Diabetes Obes Metab. 2004;6:133–56.
DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333:541–9.
Grant PJ. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care. 1996;19:64–6.
Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. Diabetes Obes Metab. 2009;11:966–77.
Tessier D, Maheux P, Khalil A, et al. Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metab Clin Exp. 1999;48:897–903.
Hollenbeck CB, Johnston P, Varasteh BB, et al. Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridaemia and non-insulin dependent diabetes by glucose tolerance test criteria. Diabete Metab. 1991;17:483–9.
Stumvoll M, Nurjhan N, Perriello G, et al. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:550–4.
Campbell IW, Menzies DG, Chalmers J, et al. One year comparative trial of metformin and glipizide in type 2 diabetes mellitus. Diabete Metab. 1994;20:394–400.
Belcher G, Lambert C, Goh KL, et al. Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide. Int J Clin Pract. 2004;58:833–7.
Wulffele MG, Kooy A, de Zeeuw D, et al. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256:1–14.
Bhalla RC, Toth KF, Tan E, et al. Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. Am J Hypertens. 1996;9:570–6.
Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344–50.
Yin M, van der Horst IC, van Melle JP, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301:H459–68.
Solskov L, Lofgren B, Kristiansen SB, et al. Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration. Basic Clin Pharmacol Toxicol. 2008;103:82–7.
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.
Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.
Solini A, Penno G, Bonora E, et al. Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study. J Am Geriatr Soc. 2013;61:1253–61. This study demonstrates that metformin treatment is independently associated with a lower prevalence of cardiovascular disease independent of age and renal function.
Roussel R, Travert F, Pasquet B, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170:1892–9.
Aguilar D, Chan W, Bozkurt B, et al. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail. 2011;4:53–8. This study demonstrates that metformin therapy is associated with lower rates of mortality in diabetic patients with heart failure.
Aguilar-Bryan L, Nichols CG, Wechsler SW, et al. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995;268:423–6.
Johanson EH, Jansson PA, Gustafson B, et al. No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes. Diabetes Metab Res Rev. 2005;21:376–81.
Salman S, Salman F, Satman I, et al. Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes. Curr Med Res Opin. 2001;16:296–306.
Jeppesen J, Zhou MY, Chen YD, et al. Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM. Diabetologia. 1994;37:781–7.
Waysbort J, Regitz G, Chaimowitz D, et al. Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus. Clin Ther. 1988;10:358–71.
Rizzo MR, Barbieri M, Grella R, et al. Repaglinide has more beneficial effect on cardiovascular risk factors than glimepiride: data from meal-test study. Diabetes Metab. 2005;31:255–60.
Monami M, Vitale V, Ambrosio ML, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther. 2012;29:736–46. This meta-analysis investigates the effects of different glucose-lowering drugs on lipid profiles.
Zhang F, **ang H, Fan Y, et al. The effects of sulfonylureas plus metformin on lipids, blood pressure, and adverse events in type 2 diabetes: a meta-analysis of randomized controlled trials. Endocrine. 2013;44:648–58.
Roumie CL, Huizinga MM, Liu X, et al. The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort. Pharmacoepidemiol Drug Saf. 2011;20:36–44.
Konya H, Hasegawa Y, Hamaguchi T, et al. Effects of gliclazide on platelet aggregation and the plasminogen activator inhibitor type 1 level in patients with type 2 diabetes mellitus. Metab Clin Exp. 2010;59:1294–9.
Manzella D, Grella R, Abbatecola AM, et al. Repaglinide administration improves brachial reactivity in type 2 diabetic patients. Diabetes Care. 2005;28:366–71.
Esposito K, Giugliano D, Nappo F, et al. Campanian Postprandial Hyperglycemia Study G. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation. 2004;110:214–9.
Phung OJ, Schwartzman E, Allen RW, et al. Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis. Diabet Med. 2013;30:1160–71. This study suggests that sulfonylurea treatment may elevate the risk of cardiovascular disease in diabetic patients.
Schramm TK, Gislason GH, Vaag A, et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J. 2011;32:1900–8. This study suggests that monotherapy with the most used insulin secretagogues is associated with increased mortality and cardiovascular risk as compared with metformin treatment.
Simpson SH, Majumdar SR, Tsuyuki RT, et al. Dose–response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ : Can Med Assoc J. 2006;174:169–74.
Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157:601–10.
Gangji AS, Cukierman T, Gerstein HC, et al. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007;30:389–94.
Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002;106:679–84.
Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. J Am Med Assoc. 2006;296:2572–81.
Khanolkar MP, Morris RH, Thomas AW, et al. Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus—an effect probably mediated by direct platelet PPARgamma activation. Atherosclerosis. 2008;197:718–24.
Patel J, Anderson RJ, Rappaport EB. Rosiglitazone monotherapy improves glycaemic control in patients with type 2 diabetes: a twelve-week, randomized, placebo-controlled study. Diabetes Obes Metab. 1999;1:165–72.
Raskin P, Rappaport EB, Cole ST, et al. Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes. Diabetologia. 2000;43:278–84.
Lebovitz HE, Dole JF, Patwardhan R, et al. Rosiglitazone Clinical Trials Study Group. Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab. 2001;86:280–8.
Phillips LS, Grunberger G, Miller E, et al. Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes. Diabetes Care. 2001;24:308–15.
Atamer Y, Atamer A, Can AS, et al. Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus. Braz J Med Biol Res. 2013;46:528–32.
Deeg MA, Buse JB, Goldberg RB, et al. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2007;30:2458–64.
Suh DC, Lee DH, McGuire M, et al. Impact of rosiglitazone therapy on the lipid profile, glycemic control, and medication costs among type 2 diabetes patients. Curr Med Res Opin. 2011;27:1623–33.
Berhanu P, Perez A, Yu S. Effect of pioglitazone in combination with insulin therapy on glycaemic control, insulin dose requirement and lipid profile in patients with type 2 diabetes previously poorly controlled with combination therapy. Diabetes Obes Metab. 2007;9:512–20.
Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005;28:1547–54.
Derosa G, D’Angelo A, Ragonesi PD, et al. Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin. Intern Med J. 2007;37:79–86.
Nicholls SJ, Tuzcu EM, Wolski K, et al. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol. 2011;57:153–9. This study shows that favorable effects of pioglitazone on the triglyceride/HDL cholesterol ratio correlate with delayed atheroma progression in diabetic patients.
Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet. 2007;370:1129–36.
Lipscombe LL, Gomes T, Levesque LE, et al. Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. J Am Med Assoc. 2007;298:2634–43.
Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. J Am Med Assoc. 2007;298:1189–95.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.
Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–89.
Komajda M, McMurray JJ, Beck-Nielsen H, et al. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Eur Heart J. 2010;31:824–31.
Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373:2125–35.
Henry RR, Lincoff AM, Mudaliar S, et al. Effect of the dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet. 2009;374(9684):126–35.
Lincoff AM, Tardif JC, Schwartz GG, et al. Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial. J Am Med Assoc. 2014;311:1515–25. This large randomized trial has shown that the dual PPAR agonist aleglitazar did not improve clinical outcomes in patients with diabetes and a recent acute coronary syndrome despite favorable effects on glycemic control and the lipid profile.
Shinoda Y, Inoue I, Nakano T, et al. Acarbose improves fibrinolytic activity in patients with impaired glucose tolerance. Metab Clin Exp. 2006;55:935–9.
Patel YR, Kirkman MS, Considine RV, et al. Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes. Diabetes Metab Res Rev. 2013;29:582–91.
Hanefeld M, Chiasson JL, Koehler C, et al. Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke. 2004;35:1073–8.
Liao Y, Takashima S, Zhao H, et al. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Cardiovasc Res. 2006;70:107–16.
Iwasa M, Kobayashi H, Yasuda S, et al. Antidiabetic drug voglibose is protective against ischemia-reperfusion injury through glucagon-like peptide 1 receptors and the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathway in rabbits. J Cardiovasc Pharmacol. 2010;55:625–34.
Hiki M, Shimada K, Kiyanagi T, et al. Single administration of alpha-glucosidase inhibitors on endothelial function and incretin secretion in diabetic patients with coronary artery disease - Juntendo University trial: effects of miglitol on endothelial vascular reactivity in type 2 diabetic patients with coronary heart disease (J-MACH). Circ J. 2010;74:1471–8.
Emoto T, Sawada T, Hashimoto M, et al. Effect of 3-month repeated administration of miglitol on vascular endothelial function in patients with diabetes mellitus and coronary artery disease. Am J Cardiol. 2012;109:42–6.
Ogawa S, Takeuchi K, Ito S. Acarbose lowers serum triglyceride and postprandial chylomicron levels in type 2 diabetes. Diabetes Obes Metab. 2004;6:384–90.
Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Am J Med. 1997;103:483–90.
Shrivastava A, Chaturvedi U, Singh SV, et al. Lipid lowering and antioxidant effect of miglitol in triton treated hyperlipidemic and high fat diet induced obese rats. Lipids. 2013;48:597–607.
Chiasson JL, Josse RG, Gomis R, et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. J Am Med Assoc. 2003;290:486–94.
Hanefeld M, Cagatay M, Petrowitsch T, et al. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004;25:10–6.
van de Laar FA, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2005;28:154–63.
Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010;375:2234–43.
Ye Y, Qian J, Castillo AC, et al. Phosphodiesterase-3 inhibition augments the myocardial infarct size-limiting effects of exenatide in mice with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2013;304:H131–41.
Nystrom T, Gutniak MK, Zhang Q, et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004;287:E1209–15.
Gaspari T, Liu H, Welungoda I, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model. Diab Vasc Dis Res. 2011;8:117–24.
Rizzo M, Chandalia M, Patti AM, et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol. 2014;13:49.
Nikolaidis LA, Mankad S, Sokos GG, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004;109:962–5.
Varanasi A, Patel P, Makdissi A, et al. Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors. Endocr Pract : Off J Am Coll Endocrinol Am Assoc Clin Endocrinologists. 2012;18:140–5.
Yu M, Moreno C, Hoagland KM, et al. Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens. 2003;21:1125–35.
Koren S, Shemesh-Bar L, Tirosh A, et al. The effect of sitagliptin versus glibenclamide on arterial stiffness, blood pressure, lipids, and inflammation in type 2 diabetes mellitus patients. Diabetes Technol Ther. 2012;14:561–7.
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. J Am Med Assoc. 2007;298:194–206.
Tokuda M, Katsuno T, Ochi F, et al. Effects of exenatide on metabolic parameters/control in obese Japanese patients with type 2 diabetes. Endocr J. 2014;61:365–72.
Schwartz EA, Koska J, Mullin MP, et al. Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type 2 diabetes mellitus. Atherosclerosis. 2010;212:217–22.
**ao C, Bandsma RH, Dash S, et al. Exenatide, a glucagon-like peptide-1 receptor agonist, acutely inhibits intestinal lipoprotein production in healthy humans. Arterioscler Thromb Vasc Biol. 2012;32:1513–9.
Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24:275–86.
Peskin BR, Shcheprov AV, Boye KS, et al. Cardiovascular outcomes associated with a new once-weekly GLP-1 receptor agonist vs. traditional therapies for type 2 diabetes: a simulation analysis. Diabetes Obes Metab. 2011;13:921–7.
Wu D, Li L, Liu C. Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: a meta-analysis. Diabetes Obes Metab. 2014;16:30–7.
Monami M, Dicembrini I, Martelli D, et al. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011;27 Suppl 3:57–64.
Monami M, Cremasco F, Lamanna C, et al. Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Exp Diabetes Res. 2011;2011:215764.
White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–35. This study demonstrates that among diabetic patients with recent acute coronary syndrome, rates of ischemic cardiovascular events are not increased with alogliptin as compared with placebo.
Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26. This study demonstrates that DPP-4 inhibition with saxagliptin does not alter rates of ischemic events, although rates of hospitalization for heart failure were increased.
Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis : NMCD. 2014;24(7):689–97.
Chao EC, Henry RR. SGLT2 inhibition - a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9:551–9.
Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin. A randomized trial. Ann Intern Med. 2012;156:405–15.
Parikh S, Wilding J, Jabbour S, Hardy E. Dapagliflozin in type 2 diabetes: effectiveness across the spectrum of disease and over time. Int J Clin Pract. 2015;69:186–98.
Bode B, Stenlöf K, Harris S, Sullivan D, Fung A, Usiskin K, et al. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes. Diabetes Obes Metab. 2015;17:294–303.
Amin NB, Wang X, Jain SM, Lee DS, Nucci G, Rusnak JM. Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes on a background of metformin. Diabetes Obes Metab. 2015;17(6):591–8.
Gerstein HC, Bosch J, Dagenais GR, et al. ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319–28.
Acknowledgments
Barbara E. Stähli was supported by the Gottfried-und-Julia-Bangerter-Rhyner Foundation, the Novartis Foundation for Medical-Biological Research (13B067), and the Swiss Foundation for Medical-Biological Scholarships (SSMBS; No P3SMP3_151740/1). Cathérine Gebhard was supported by the Novartis Foundation for Medical-Biological Research and the Swiss Foundation for Medical-Biological Scholarships (SSMBS; No 142741). Dr. Tardif holds the Canada Research Chair in translational and personalized medicine and the University of Montreal endowed research chair in atherosclerosis.
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Barbara E. Stähli and Catherine Gebhard declare that they have no conflict of interest.
Jean-Claude Tardif has received grant support from Astra-Zeneca, Roche, Sanofi, and Valeant and has received honoraria from Roche, Sanofi, and Valeant.
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Stähli, B.E., Gebhard, C. & Tardif, JC. Lipid Effects and Cardiovascular Disease Risk Associated with Glucose-Lowering Medications. Curr Cardiol Rep 17, 55 (2015). https://doi.org/10.1007/s11886-015-0608-6
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DOI: https://doi.org/10.1007/s11886-015-0608-6