What is type 2 diabetes?
Insulin is a hormone that is produced by the pancreas to help regulate the amount of glucose in the blood. Type 2 diabetes is caused by a lack of insulin production, or an inability to use the insulin that is produced by the body. As a result, glucose cannot be transported into cells and used for energy.
Unlike type 1 diabetes, type 2 diabetes is typically diagnosed during adulthood. Risk factors include family history, age, ethnicity, and obesity.
Dietary and lifestyle changes are initial strategies that can be used to control type 2 diabetes; however, medications are necessary if blood glucose levels cannot be controlled with these measures alone.
How is type 2 diabetes diagnosed?
Your doctor will diagnose diabetes, usually using a fasting glucose blood test or an A1c test. These tests will let your doctor know how much glucose is present in your blood, these levels will indicate whether or not you have diabetes.
Current treatment for type 2 diabetes
Multiple options are available as a treatment for type 2 diabetes. Depending on your response to initial treatment your doctor may prescribe single or multiple therapies to keep your diabetes under control. Your doctor may also recommend lifestyle changes – dietary and physical activity – to help manage your diabetes.
Metformin is an oral glucose-lowering medication that is typically used as a first-line treatment for type 2 diabetes. Metformin has been used for decades as a diabetes treatment and has a good safety profile at a relatively low cost.
Unlike other diabetes treatments, metformin does not cause hypoglycemia as a side effect.
Traditionally, metformin has been thought to induce its glucose-lowering effect by acting to decrease glucose production by the liver. However, more recent studies suggest that this might not be the only way this drug works. The effects of metformin may also depend on the length of treatment and the dosages used.
Metformin is also often used in combination with other diabetes drugs, most commonly sulfonylureas.
Some of the side effects associated with Metformin include diarrhea, muscle weakness, abdominal pain, and low vitamin B12 levels.
Second-generation sulfonylureas (glipizide, glyburide, and glimepiride) have significantly fewer side effects than first-generation drugs in this class. These drugs work by increasing the amount of insulin that is released from the pancreas and improving insulin resistance.
A significant side effect to monitor in patients taking sulfonylureas is hypoglycemia. Other side effects can include weight gain, skin reactions, and stomach disturbances.
The thiazolidinediones rosiglitazone and pioglitazone are oral medications that are used to reduce blood glucose by enhancing glucose uptake in patients with type 2 diabetes.
Although these agents have a low risk of hypoglycemia, they have been associated with an increased risk of heart failure, leading to the limited use of rosiglitazone.
Insulin treatment may be required for to make up for the lack of insulin produced by the pancreas in type 2 diabetes patients. Insulin can be given alone or in combination with other diabetes medications.
There are multiple formulations of insulin available for treating type 2 diabetes, which include long-acting insulin formulations (for example degludec or detemir).
These formulations provide more consistent insulin concentrations that better mimic normal insulin production.
Patients should be properly trained on how to administer insulin injections and what side effects to look out for. There is a significant risk of hypoglycemia in patients taking insulin, which should be carefully monitored and promptly treated if it should occur.
Glucagon-like peptide 1 receptor agonists
Glucagon-like peptide 1 (GLP-1) receptor agonists also act to lower blood glucose levels. This class of drugs acts to increase the amount of insulin that is produced after a meal, and by reducing the amount of glucagon that is released by the pancreas. These drugs are also able to slow down the rate that the stomach empties after a meal, which slows down the absorption of glucose into the blood. This results in a ‘full’ feeling for a more extended period of time, which is likely responsible for the association of these drugs with weight loss.
There are several GLP-1 receptor agonists currently approved for type 2 diabetes treatment, these include liraglutide, exenatide, dulaglutide, and semaglutide.
Treatment with GLP-1 receptor agonists has also been associated with reductions in blood pressure and weight loss. These drugs also pose a low risk of hypoglycemia.
Importantly, this drug class has also been associated with beneficial cardiovascular effects, with some clinical trials reporting a reduction in cardiovascular events and reduced risk of cardiovascular mortality.
Some of the side effects associated with GLDP-1 receptor agonists include nausea, vomiting, diarrhea, and constipation.
Sodium-glucose cotransporter 2 inhibitors
Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) are among the newest type of treatment for type 2 diabetes. These drugs include canagliflozin, dapagliflozin, and empagliflozin.
These drugs act in a different way from other diabetes medications; they prevent the kidneys from re-absorbing glucose, resulting in the removal of glucose from the body via the urine.
Weight loss and blood pressure reductions have been seen with SGLT2 inhibitors. Weight loss effects are even greater when combined with metformin.
Clinical trials with empagliflozin have reported reduced cardiovascular events in patients with type 2 diabetes who also have a history of cardiovascular disease.
Some common side effects associated with SGLT2 inhibitors include an increased risk of infection, joint pain, and nausea.
Dipeptidyl peptidase-4 inhibitors
Another new class of drugs to treat type 2 diabetes is the dipeptidyl peptidase-4 (DPP-4) inhibitors. These drugs are able to reduce glucose levels by blocking DPP-4, which increases incretin levels and increases the secretion of insulin. DPP-4 inhibitors include stigaliptin, alogliptin, saxagliptin, and linagliptin.
Studies have suggested that these drugs have a lower risk of hyperglycemia, however, do not appear to be associated with weight loss. DPP-4 inhibitors have not demonstrated significant cardiovascular or renal benefits despite large clinical trials.
Typical side effects of these medications include nausea, diarrhea, and flu-like symptoms, and can cause some skin reactions.
Sanchez-Rangel, E., Inzucchi, S.E. Metformin: clinical use in type 2 diabetes. Diabetologia 60, 1586–1593 (2017). https://doi.org/10.1007/s00125-017-4336-x
Rena, G., Hardie, D.G. & Pearson, E.R. The mechanisms of action of metformin. Diabetologia 60, 1577–1585 (2017). https://doi.org/10.1007/s00125-017-4342-z
Boyle JG, Livingstone R, Petrie JR. Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review. Clin Sci (Lond). 2018;132(15):1699-1709. Published 2018 Aug 16. doi:10.1042/CS20171299
Bahtiyar G, Pujals-Kury J, Sacerdote A. Cardiovascular Effects of Different GLP-1 Receptor Agonists in Patients with Type 2 Diabetes. Curr Diab Rep. 2018;18(10):92. Published 2018 Aug 31. doi:10.1007/s11892-018-1043-z
Ninčević V, Omanović Kolarić T, Roguljić H, Kizivat T, Smolić M, Bilić Ćurčić I. Renal Benefits of SGLT 2 Inhibitors and GLP-1 Receptor Agonists: Evidence Supporting a Paradigm Shift in the Medical Management of Type 2 Diabetes. Int J Mol Sci. 2019;20(23):5831. Published 2019 Nov 20. doi:10.3390/ijms20235831
Freeland B, Farber MS. A Review of Insulin for the Treatment of Diabetes Mellitus. Home Healthc Now. 2016;34(8):416-423. doi:10.1097/NHH.0000000000000446
Arnold SV, Inzucchi SE, Echouffo-Tcheugui JB, et al. Understanding Contemporary Use of Thiazolidinediones. Circ Heart Fail. 2019;12(6):e005855. doi:10.1161/CIRCHEARTFAILURE.118.005855
Luna B, Feinglos MN. Oral agents in the management of type 2 diabetes mellitus. Am Fam Physician. 2001;63(9):1747-1756.
Molly G. Minze*, Kayley J. Will*, Brian T. Terrell, Robin L. Black and Brian K. Irons, “Benefits of SGLT2 Inhibitors Beyond Glycemic Control – A Focus on Metabolic, Cardiovascular and Renal Outcomes”, Current Diabetes Reviews (2018) 14: 509. https://doi.org/10.2174/1573399813666170816142351
Hanssen NM, Jandeleit-Dahm KA. Dipeptidyl peptidase-4 inhibitors and cardiovascular and renal disease in type 2 diabetes: What have we learned from the CARMELINA trial?. Diab Vasc Dis Res. 2019;16(4):303-309. doi:10.1177/1479164119842339
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