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Oral Glucose-Lowering Agent Treatments in Type 2 Diabetes Mellitus

Year 2021, , 1 - 5, 29.01.2021
https://doi.org/10.46310/tjim.815794

Abstract

Type 2 diabetes is manifested by impaired insulin secretion in pancreatic beta cells, increased glucagon secretion in alpha cells, and generally has a history of insulin resistance. The treatment of glucose metabolism disorder and the resulting hyperglycemia constitute an important part of the treatment of type 2 diabetes. Glycemic targets can be targeted with A1C <7% to reduce the risk of micro and macrovascular complications in eligible patients, and A1C <6.5% to reduce the risk of diabetic chronic renal failure and retinopathy in those with low risk of hypoglycemia. We can consider the treatment of hyperglycemia in two components; lifestyle changes and glucose-lowering agent therapy.

References

  • American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes. 2020 Diabetes Care 2020;43(Suppl.1):14-31
  • Kahn SE. The relative contributions of insulin resistance and beta‐cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003;46:3-19.
  • Koenig RJ, Peterson CM, Jones RL, et al. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N Engl J Med. 1976;295:417-20.
  • 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.
  • American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43:S98.
  • Vijan S, Sussman JB, Yudkin JS, et al. Effect of patients’ risks and preferences on health gains with plasma glucose level lowering in type 2 diabetes mellitus. JAMA Intern Med 2014;174:1227-34.
  • Vaag AA. Glycemic control and prevention of microvascular and macrovascular disease in the Steno 2 study. Endocr Pract. 2006;12:89-92
  • Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:4909.
  • Chong S, Ding D, Byurn R, et al. Lifestyle changes after a diagnosis of type 2 diabetes. Diabetes Spectr. 2017;30:43-50.
  • Zinman B, Ruderman N, Campaigne BN, et al. Physical activity/exercise and diabetes mellitus. Diabetes Care. 2003;26(suppl1):73-7.
  • Mulcahy K, Maryniuk M, Peeples M, et al. Diabetes self-management education core outcomes measures. Diabetes Educ 2003;29:768–84.
  • Zhou G Myers R, Li Y et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-74.
  • Hundal RS Krssak M, Dufour S et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-9.
  • Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011; 34:1431-1437.
  • de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. 2010; BMJ 340:2181.
  • Aroda VR, Edelstein SL, Goldberg RB, et al. Diabetes Prevention Program Research Group. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016;101:1754-61
  • Cahn A, Cefalu WT. Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care 2016;39 (Suppl.2):137-45
  • Phung OJ, Sobieraj DM, Engel SS, et al. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2014;16:410-17
  • Das SR, Everett BM, Birtcher KK, et al. 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018;72:3200.
  • Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008;168:2070-80
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
  • Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-57.
  • Kim Y, Babu AR. Clinical potential of sodium-glucose co-transporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes. 2012;5:313-27.
  • Wanner C, Lachin JM, Inzucchi SE, et al. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 2018;137:119-29.
  • Perkovic V, Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 2018;6:691-704.
  • Li DD, Wang TS, Shen S, et al. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2017;19:348-355.
  • Nancy A. Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4), Best Practice & Research Clinical Endocrinology & Metabolism 23,4,2009;479-86
  • Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 dibetes. N Engl J Med 2015;373:232-42.
  • 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.
  • 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.
  • Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019;42:1724-32.
  • Pieber TR, Bode B,Mertens A, et al. PIONEER 7 investigators. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol 2019;7:528-39
  • Husain M, Birkenfeld AL, Donsmark M, et al. PIONEER 6 Investigators. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019;381:841-51.
  • Rodbard HW. Rosenstock J, Canani LH, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial Diabetes Care 2019;42:2272-81.
  • Kahn CR, Chen L, Cohen SE. Unraveling the mechanism of action of thiazolidinediones, J Clin Invest. 2000;106(11):1305-7.
  • Smith U. Pioglitazone: mechanism of action. International Journal of Clinical Practice. 2001 Supplement (121):13-8
  • Al Majali, K. et al. The efect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia. 2006;49,527-37.
  • Fonseca, V. Efect of thiazolidinediones on body weight in patients with diabetes mellitus. Am. J. Med. 2003;115,42-8.
  • Lincof AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298,1180-88.
  • Scheen AJ. Outcomes and lessons from the PROactive study. Diabetes Research and Clinical Practice. 2012;98(2):175-86.
  • Filipova E, Uzunova K, Kalinov K, et al. Pioglitazone and the risk of bladder cancer: a meta-analysis. Diabetes Ter 2017;8,705-26.
  • Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a metaanalysis. CMAJ 2009;180:32-39.
  • Meier C, Kraenzlin ME, Bodmer M, et al. Use of thiazolidinediones and fracture risk. Arch Intern Med 2008;168:820-25.
  • Seino S Cell signalling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea. Diabetologia 2012;55(8):2096-108.
  • Rao AD, Kuhadiya N, Reynolds K, et al. Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality? A meta-analysis of observational studies. Diabetes Care 2008;31:1672-8.
  • Shorr RI, Ray WA, Daugherty JR, et al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157:1681-6.
  • Derosa G, Mugellini A, Ciccarelli L, et al. Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one‐year, randomized, double‐blind assessment of metabolic parameters and cardiovascular risk factor. Clinical Therapeutics 2003;25(2):472‐84.
  • Hanefeld M, Fischer S, Schulze J, et al. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Diabetes Care 1991;14:732-737.
  • Coniff RF, Shapiro JA, Timothy B, et al. Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. Arch Intern Med 1994;154:2442-48.
Year 2021, , 1 - 5, 29.01.2021
https://doi.org/10.46310/tjim.815794

Abstract

References

  • American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes. 2020 Diabetes Care 2020;43(Suppl.1):14-31
  • Kahn SE. The relative contributions of insulin resistance and beta‐cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003;46:3-19.
  • Koenig RJ, Peterson CM, Jones RL, et al. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N Engl J Med. 1976;295:417-20.
  • 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.
  • American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43:S98.
  • Vijan S, Sussman JB, Yudkin JS, et al. Effect of patients’ risks and preferences on health gains with plasma glucose level lowering in type 2 diabetes mellitus. JAMA Intern Med 2014;174:1227-34.
  • Vaag AA. Glycemic control and prevention of microvascular and macrovascular disease in the Steno 2 study. Endocr Pract. 2006;12:89-92
  • Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:4909.
  • Chong S, Ding D, Byurn R, et al. Lifestyle changes after a diagnosis of type 2 diabetes. Diabetes Spectr. 2017;30:43-50.
  • Zinman B, Ruderman N, Campaigne BN, et al. Physical activity/exercise and diabetes mellitus. Diabetes Care. 2003;26(suppl1):73-7.
  • Mulcahy K, Maryniuk M, Peeples M, et al. Diabetes self-management education core outcomes measures. Diabetes Educ 2003;29:768–84.
  • Zhou G Myers R, Li Y et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-74.
  • Hundal RS Krssak M, Dufour S et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 2000;49:2063-9.
  • Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011; 34:1431-1437.
  • de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. 2010; BMJ 340:2181.
  • Aroda VR, Edelstein SL, Goldberg RB, et al. Diabetes Prevention Program Research Group. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016;101:1754-61
  • Cahn A, Cefalu WT. Clinical considerations for use of initial combination therapy in type 2 diabetes. Diabetes Care 2016;39 (Suppl.2):137-45
  • Phung OJ, Sobieraj DM, Engel SS, et al. Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2014;16:410-17
  • Das SR, Everett BM, Birtcher KK, et al. 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2018;72:3200.
  • Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008;168:2070-80
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
  • Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-57.
  • Kim Y, Babu AR. Clinical potential of sodium-glucose co-transporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes. 2012;5:313-27.
  • Wanner C, Lachin JM, Inzucchi SE, et al. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 2018;137:119-29.
  • Perkovic V, Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 2018;6:691-704.
  • Li DD, Wang TS, Shen S, et al. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2017;19:348-355.
  • Nancy A. Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4), Best Practice & Research Clinical Endocrinology & Metabolism 23,4,2009;479-86
  • Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 dibetes. N Engl J Med 2015;373:232-42.
  • 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.
  • 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.
  • Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019;42:1724-32.
  • Pieber TR, Bode B,Mertens A, et al. PIONEER 7 investigators. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol 2019;7:528-39
  • Husain M, Birkenfeld AL, Donsmark M, et al. PIONEER 6 Investigators. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019;381:841-51.
  • Rodbard HW. Rosenstock J, Canani LH, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial Diabetes Care 2019;42:2272-81.
  • Kahn CR, Chen L, Cohen SE. Unraveling the mechanism of action of thiazolidinediones, J Clin Invest. 2000;106(11):1305-7.
  • Smith U. Pioglitazone: mechanism of action. International Journal of Clinical Practice. 2001 Supplement (121):13-8
  • Al Majali, K. et al. The efect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia. 2006;49,527-37.
  • Fonseca, V. Efect of thiazolidinediones on body weight in patients with diabetes mellitus. Am. J. Med. 2003;115,42-8.
  • Lincof AM, Wolski K, Nicholls SJ, et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298,1180-88.
  • Scheen AJ. Outcomes and lessons from the PROactive study. Diabetes Research and Clinical Practice. 2012;98(2):175-86.
  • Filipova E, Uzunova K, Kalinov K, et al. Pioglitazone and the risk of bladder cancer: a meta-analysis. Diabetes Ter 2017;8,705-26.
  • Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a metaanalysis. CMAJ 2009;180:32-39.
  • Meier C, Kraenzlin ME, Bodmer M, et al. Use of thiazolidinediones and fracture risk. Arch Intern Med 2008;168:820-25.
  • Seino S Cell signalling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea. Diabetologia 2012;55(8):2096-108.
  • Rao AD, Kuhadiya N, Reynolds K, et al. Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality? A meta-analysis of observational studies. Diabetes Care 2008;31:1672-8.
  • Shorr RI, Ray WA, Daugherty JR, et al. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997; 157:1681-6.
  • Derosa G, Mugellini A, Ciccarelli L, et al. Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one‐year, randomized, double‐blind assessment of metabolic parameters and cardiovascular risk factor. Clinical Therapeutics 2003;25(2):472‐84.
  • Hanefeld M, Fischer S, Schulze J, et al. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Diabetes Care 1991;14:732-737.
  • Coniff RF, Shapiro JA, Timothy B, et al. Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. Arch Intern Med 1994;154:2442-48.
There are 49 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Editorial
Authors

Şazi İmamoğlu This is me 0000-0002-9610-5880

Publication Date January 29, 2021
Submission Date October 20, 2020
Acceptance Date November 4, 2020
Published in Issue Year 2021

Cite

EndNote İmamoğlu Ş (January 1, 2021) Oral Glucose-Lowering Agent Treatments in Type 2 Diabetes Mellitus. Turkish Journal of Internal Medicine 3 1 1–5.

e-ISSN: 2687-4245 

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