1. bookVolume 60 (2022): Issue 1 (March 2022)
Journal Details
First Published
30 Mar 2015
Publication timeframe
4 times per year
access type Open Access

A practical review of diabetes mellitus type 2 treatment in primary care

Published Online: 17 Mar 2022
Page range: 14 - 23
Received: 18 Jun 2021
Journal Details
First Published
30 Mar 2015
Publication timeframe
4 times per year

The treatment of diabetes mellitus type 2 (DM2) is becoming more complex as new medications are approved. Primary care providers must maintain their medical knowledge on emerging medications for best patient care. This review simplifies the non-insulin treatments of diabetes with an emphasis on the cardio-renal protectants, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1).


1. SAEEDI P., PETERSOHN I., SALPEA P., MALANDA B., KARURANGA S., UNWIN N., et al. IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.10.1016/j.diabres.2019.10784331518657Search in Google Scholar

2. MOTA M., POPA SG., MOTA E., MITREA A., CATRINOIU D., CHETA DM., et al. Prevalence of diabetes mellitus and prediabetes in the adult Romanian population: PREDATORR study. J Diabetes. 2016;8(3):336–44.10.1111/1753-0407.1229725850521Search in Google Scholar

3. TSOUTSOUKI J., WUNNA W., CHOWDHURY A., CHOWDHURY TA. Advances in the management of diabetes: therapies for type 2 diabetes. Postgrad Med J. 2020;96(1140):610–618.10.1136/postgradmedj-2019-13740432467106Search in Google Scholar

4. SHIN JL. Second-line Glucose-Lowering Therapy in Type 2 Diabetes Mellitus. Curr Diab Rep. 2019;19(8):54.10.1007/s11892-019-1171-031286271Search in Google Scholar

5. CHARBONNEL B., DORMANDY K., ERDMANN E., MASSI-BENEDETTI M., SKENE A. PROactive Study Group. The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care. 2004;27(7):1647–53.10.2337/diacare.27.7.164715220241Search in Google Scholar

6. AMERICAN DIABETES ASSOCIATION. Standards of Medical Care in Diabetes-2021 Abridged for Primary Care Providers. Clin Diabetes. 2021;39(1):14–43.10.2337/cd21-as01783961333551551Search in Google Scholar

7. LOOK AHEAD RESEARCH GROUP., WING RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170(17):1566–75.Search in Google Scholar

8. SHANTHA GP., KUMAR AA., KAHAN S., CHESKIN LJ. Association between glycosylated hemoglobin and intentional weight loss in overweight and obese patients with type 2 diabetes mellitus: a retrospective cohort study. Diabetes Educ. 2012;38(3):417–26.10.1177/014572171244329322508341Search in Google Scholar

9. KUMAR AA., PALAMANER SUBASH SHANTHA G., KAHAN S., SAMSON RJ., BODDU ND., CHESKIN LJ. Intentional weight loss and dose reductions of anti-diabetic medications-a retrospective cohort study. PLoS One. 2012;7(2):e32395.10.1371/journal.pone.0032395328809222384240Search in Google Scholar

10. GUMMESSON A., NYMAN E., KNUTSSON M., KARPEFORS M. Effect of weight reduction on glycated haemoglobin in weight loss trials in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(9):1295–1305.10.1111/dom.1297128417575Search in Google Scholar

11. COLBERG SR., SIGAL RJ., YARDLEY JE., RIDDELL MC., DUNSTAN DW., DEMPSEY PC., et al. Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care. 2016;39(11):2065–2079.10.2337/dc16-1728690841427926890Search in Google Scholar

12. HELLER SR. ADVANCE Collaborative Group. A summary of the ADVANCE Trial. Diabetes Care. 2009;32 Suppl 2 (Suppl 2): S357–61.10.2337/dc09-S339Search in Google Scholar

13. COSENTINO F., GRANT PJ., ABOYANS V., BAILEY CJ., CERIELLO A., DELGADO V., et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255–323.10.1093/eurheartj/ehz486Search in Google Scholar

14. BAILEY CJ., MARX N. Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials. Diabetes Obes Metab. 2019;21(1):3–14.10.1111/dom.13492Search in Google Scholar

15. KALYANI RR. Glucose-Lowering Drugs to Reduce Cardiovascular Risk in Type 2 Diabetes. N Engl J Med. 2021;384(13):1248–1260.10.1056/NEJMcp2000280Search in Google Scholar

16. RAVAL AD., VYAS A. National Trends in Diabetes Medication Use in the United States: 2008 to 2015. J Pharm Pract. 2020;33(4):433–442.10.1177/0897190018815048Search in Google Scholar

17. LIBIANTO R., DAVIS TM., EKINCI EI. Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes. Med J Aust. 2020;212(3):133–139.10.5694/mja2.50472Search in Google Scholar

18. NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (UK). Type 2 diabetes in adults: management. London: National Institute for Health and Care Excellence (UK); 2015.Search in Google Scholar

19. RENA G., HARDIE DG., PEARSON ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577–1585.10.1007/s00125-017-4342-zSearch in Google Scholar

20. FORETZ M., GUIGAS B., VIOLLET B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol. 2019;15(10):569–589.10.1038/s41574-019-0242-2Search in Google Scholar

21. GARBER AJ., DUNCAN TG., GOODMAN AM., MILLS DJ., ROHLF JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med. 1997;103(6):491–497.10.1016/S0002-9343(97)00254-4Search in Google Scholar

22. MARIANO F., BIANCONE L. Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist J Nephrol. 2020. Epub ahead of print.10.1007/s40620-020-00941-8835776233373028Search in Google Scholar

23. SCHEEN AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015;75(1):33–59.10.1007/s40265-014-0337-ySearch in Google Scholar

24. DESOUZA CV., GUPTA N., PATEL A. Cardiometabolic Effects of a New Class of Antidiabetic Agents. Clin Ther. 2015;37(6):1178–1194.10.1016/j.clinthera.2015.02.016Search in Google Scholar

25. VASILAKOU D., KARAGIANNIS T., ATHANASIADOU E., MAINOU M., LIAKOS A., BEKIARI E., et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262–74.10.7326/0003-4819-159-4-201308200-00007Search in Google Scholar

26. LIBIANTO R., DAVIS TM., EKINCI EI. Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes. Med J Aust. 2020;212(3):133–139.10.5694/mja2.50472Search in Google Scholar

27. RABIZADEH S., NAKHJAVANI M., ESTEGHAMATI A. Cardiovascular and Renal Benefits of SGLT2 Inhibitors: A Narrative Review. Int J Endocrinol Metab. 2019;17(2):e84353.10.5812/ijem.84353Search in Google Scholar

28. CHEEN AJ. An update on the safety of SGLT2 inhibitors. Expert Opin Drug Saf. 2019;18(4):295–311.10.1080/14740338.2019.1602116Search in Google Scholar

29. HINNEN D. Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes. Diabetes Spectr. 2017;30(3):202–210.10.2337/ds16-0026Search in Google Scholar

30. HTIKE ZZ., ZACCARDI F., PAPAMARGARITIS D., WEBB DR., KHUNTI K., DAVIES MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524–536.10.1111/dom.12849Search in Google Scholar

31. KRISTENSEN SL., RØRTH R., JHUND PS., DOCHERTY KF., SATTAR N., PREISS D., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–785.10.1016/S2213-8587(19)30249-9Search in Google Scholar

32. MARSO SP., BAIN SC., CONSOLI A., ELIASCHEWITZ FG., JÓDAR E., LEITER LA., et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834–1844.10.1056/NEJMoa160714127633186Search in Google Scholar

33. WILDING JPH., BATTERHAM RL., CALANNA S., DAVIES M., VAN GAAL LF., LINGVAY I., et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989.10.1056/NEJMoa203218333567185Search in Google Scholar

34. FILIPPATOS TD., PANAGIOTOPOULOU TV., ELISAF MS. Adverse Effects of GLP-1 Receptor Agonists. Rev Diabet Stud. 2014;11(3-4):202–230.10.1900/RDS.2014.11.202539728826177483Search in Google Scholar

35. STOGAARD H., COLD F., GLUUD LL., VILSBØLL T., KNOP FK. Glucagon-like peptide-1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(6):906–908.10.1111/dom.1288528105738Search in Google Scholar

36. PINTO LC., FALCETTA MR., RADOS DV., LEITÃO CB. GROSS JL. Glucagon-like peptide-1 receptor agonists and pancreatic cancer: a meta-analysis with trial sequential analysis. Sci Rep. 2019;9(1):2375.10.1038/s41598-019-38956-2638278030787365Search in Google Scholar

37. CAO C., YANG S., ZHOU Z. GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials. Endocrine. 2019;66(2):157–165.10.1007/s12020-019-02055-z31420784Search in Google Scholar

38. LEROITH D., BIESSELS GJ., BRAITHWAITE SS., CASANUEVA FF., DRAZNIN B., HALTER JB., et al. Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104(5):1520–1574.10.1210/jc.2019-00198727196830903688Search in Google Scholar

39. LI CJ., ZHANG JY., YU DM., ZHANG QM. Adding glimepiride to current insulin therapy increases high-molecular weight adiponectin levels to improve glycemic control in poorly controlled type 2 diabetes. Diabetol Metab Syndr. 2014 Mar 20;6(1):41.10.1186/1758-5996-6-41399447024650537Search in Google Scholar

40. KABADI M., KABADI U. Efficacy of Sulfonylureas with Insulin in Type 2 Diabetes Mellitus. Ann Pharmacother. 2003;37(11):1572–6.10.1345/aph.1C49214565810Search in Google Scholar

41. SOLA D., ROSSI L., SCHIANCA GP., MAFFIOLI P., BIGLIOCCA M., MELLA R., et al. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015;11(4):840–8.10.5114/aoms.2015.53304454803626322096Search in Google Scholar

42. RAO AD., KUHADIYA N., REYNOLDS K., FONSECA VA. 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(8):1672–1678.10.2337/dc08-0167249462318458139Search in Google Scholar

43. HAUNER H. The mode of action of thiazolidinediones. Diabetes Metab Res Rev. 2002;18 Suppl 2:S10–S15.10.1002/dmrr.24911921433Search in Google Scholar

44. HUSSEIN Z., WENTWORTH JM., NANKERVIS AJ., PROIETTO J., COLMAN PG. Effectiveness and side effects of thiazolidinediones for type 2 diabetes: real-life experience from a tertiary hospital. Med J Aust. 2004;181(10):536–539.10.5694/j.1326-5377.2004.tb06441.xSearch in Google Scholar

45. GOLDBERG RG. The new clinical trials with thiazolidinediones-DREAM, ADOPT, and CHICAGO: promises fulfilled? Curr Opin Lipidol. 2007;18(4):435–442.10.1097/MOL.0b013e32821f604c17620861Search in Google Scholar

46. DELLA-MORTE D., PALMIROTTA R., REHNI AK., PASTORE D., CAPUANI B., PACIFICI F., et al. Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors. Pharmacogenomics. 2014;15(16):2063–82.10.2217/pgs.14.162431421325521362Search in Google Scholar

47. RIZOS CV., ELISAF MS., MIKHAILIDIS DP., LIBEROPOULOS EN. How safe is the use of thiazolidinediones in clinical practice? Expert Opin Drug Saf. 2009;8(1):15–32.10.1517/1474033080259782119236215Search in Google Scholar

48. THORNBERRY NA., GALLWITZ B. Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4). Best Pract Res Clin Endocrinol Metab. 2009;23(4):479–486.10.1016/j.beem.2009.03.00419748065Search in Google Scholar

49. AHRÉN B. Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs. 2008;13(4):593–607.10.1517/1472821080258412619046129Search in Google Scholar

50. LAMOS EM., HEDRINGTON M., DAVIS SN. An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors. Expert Opin Drug Saf. 2019;18(8):691–701.10.1080/14740338.2019.162682331150300Search in Google Scholar

51. SCIRICA BM, BHATT DL., BRAUNWALD E. STEG PG., DAVIDSON J., HIRSHBERG B., et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317–26.10.1056/NEJMoa130768423992601Search in Google Scholar

52. MEN P., HE N., SONG C., ZHAI S. Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis. Diabetes Metab. 2017;43(6):493–500.10.1016/j.diabet.2017.05.01328778563Search in Google Scholar

53. HOFFMAN J., SPENGLER M. Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care. 1994;17(6):561–566.10.2337/diacare.17.6.5618082525Search in Google Scholar

54. MENEILLY GS., RYAN EA., RADZIUK J., LAU DC., YALE JF., MORAIS J., et al. Effect of acarbose on insulin sensitivity in elderly patients with diabetes. Diabetes Care. 2000;23(8):1162–7.10.2337/diacare.23.8.116210937515Search in Google Scholar

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