Sulfonylureas can be taken alone or with metformin, pioglitazone a thiazolidinedione , or insulin. This class of medicines includes rosiglitazone and pioglitazone.

These medicines help your body respond better to insulin. Rosiglitazone and pioglitazone can be used alone or in combination with other diabetes medicines. People taking rosiglitazone and pioglitazone also need periodic liver tests. There are two medicines in this group: repaglinide and nateglinide.

Both of these lower your blood glucose by prompting the pancreas to release more insulin. These drugs work quickly and do not stay in your system long. So they are a good option if your meal schedule varies or is unpredictable. They also cause less weight gain than other oral diabetes medicines.

Alpha-glucosidase inhibitors help control blood sugar levels by preventing the digestion of carbohydrates. Carbohydrates include starchy foods like potatoes and corn. They also include most grains bread, rice, crackers, cereal and sugary sweets. The two medicines in this group are acarbose and miglitol.

These medicines may cause bloating, nausea, diarrhea, and flatulence gas. A newer class of diabetes medication, SGLT2, includes three medicines: canagliflozin, dapagliflozin, and empagliflozin.

These drugs remove extra sugar from your body by sending the sugar out through your kidneys into your urine. They also cause your body to be more sensitive to insulin.

The most common side effects caused by SGLT2 are vaginal yeast infections and urinary tract infections.

There are four medicines in this class of drugs. They are sitagliptin, saxagliptin, linagliptin, and alogliptin. DPP-4 inhibitors help your pancreas release more insulin after you eat. These medicines also tell your liver to release less glucose. Some side effects from taking DPP-4 inhibitors may include nausea and diarrhea.

This class of drugs pulls double duty. The medicine in this class, colesevelam, lowers cholesterol and reduces blood sugar levels. So it could be a good choice if you have diabetes and high cholesterol levels. And because these drugs are not absorbed in the blood stream, they may be the best choice for someone who also has liver problems and cannot take some of the other diabetes medicines.

Side effects from bile acid sequestrants can include constipation and flatulence gas. Managing your blood sugar level is critical to your overall health. Often the focus is on keeping blood sugar levels low. But if they are too low, it can put you at risk, too.

Among common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain. Typical reduction in glycated hemoglobin A1C values for metformin is 1. Metformin is usually the first-line medication used for treatment of type 2 diabetes.

In general, it is prescribed at initial diagnosis in conjunction with exercise and weight loss, as opposed to in the past, where it was prescribed after diet and exercise had failed.

There is an immediate-release as well as an extended-release formulation, typically reserved for patients experiencing gastrointestinal side-effects. It is also available in combination with other oral diabetic medications.

Thiazolidinediones TZDs , also known as "glitazones," bind to PPARγ , peroxisome proliferator activated receptor γ , a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on peroxisome proliferator responsive elements PPRE. The final result is better use of glucose by the cells.

These drugs also enhance PPAR-α activity and hence lead to a rise in HDL and some larger components of LDL. Typical reductions in glycated hemoglobin A1C values are 1. Some examples are:. Multiple retrospective studies have resulted in a concern about rosiglitazone's safety, although it is established that the group, as a whole, has beneficial effects on diabetes.

The greatest concern is an increase in the number of severe cardiac events in patients taking it. The ADOPT study showed that initial therapy with drugs of this type may prevent the progression of disease, [13] as did the DREAM trial.

However, they are less preferred than GLP-1 agonists or SGLT2 inhibitors, especially in patients with cardiovascular disease which liraglutide , empagliflozin , and canagliflozin are all FDA approved to treat.

Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate the issue, and several other reports have failed to conclude the controversy.

This weak evidence for adverse effects has reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control. In contrast, at least one large prospective study, PROactive 05, has shown that pioglitazone may decrease the overall incidence of cardiac events in people with type 2 diabetes who have already had a heart attack.

The LYN kinase activator tolimidone has been reported to potentiate insulin signaling in a manner that is distinct from the glitazones.

Secretagogues are drugs that increase output from a gland, in the case of insulin from the pancreas. Sulfonylureas were the first widely used oral anti-hyperglycemic medications. They are insulin secretagogues , triggering insulin release by inhibiting the K ATP channel of the pancreatic beta cells.

Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side-effects.

All may cause weight gain. Current clinical practice guidelines from the AACE rate sulfonylureas as well as glinides below all other classes of antidiabetic drugs in terms of suggested use as first, second, or third line agents - this includes bromocriptine , the bile acid sequestrant colesevelam , α-glucosidase inhibitors , TZDs glitazones , and DPP-4 inhibitors gliptins.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are useful only in type 2 diabetes, as they work by stimulating endogenous release of insulin.

They work best with patients over 40 years old who have had diabetes mellitus for under ten years. They cannot be used with type 1 diabetes, or diabetes of pregnancy.

They can be safely used with metformin or glitazones. The primary side-effect is hypoglycemia , which appears to happen more commonly with sulfonylureas than with other treatments.

A Cochrane systematic review from showed that treatment with Sulphonylurea did not improve control of glucose levels more than insulin at 3 nor 12 months of treatment.

Typical reductions in glycated hemoglobin A1C values for second-generation sulfonylureas are 1. Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues.

They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped. Typical reductions in glycated hemoglobin A1C values are 0. Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity.

These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance , but can be helpful in combination with other agents in type 2 diabetes.

These medications are rarely used in the United States because of the severity of their side-effects flatulence and bloating. They are more commonly prescribed in Europe. They do have the potential to cause weight loss by lowering the amount of sugar metabolized.

Incretins are also insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are glucagon-like peptide-1 GLP-1 and gastric inhibitory peptide glucose-dependent insulinotropic peptide, GIP.

Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 DPP Glucagon-like peptide GLP agonists bind to a membrane GLP receptor. Endogenous GLP has a half-life of only a few minutes, thus an analogue of GLP would not be practical. As of , the AACE lists GLP-1 agonists, along with SGLT2 inhibitors, as the most preferred anti-diabetic agents after metformin.

Liraglutide in particular may be considered first-line in diabetic patients with cardiovascular disease, as it has received FDA approval for reduction of risk of major adverse cardiovascular events in patients with type 2 diabetes.

These agents may also cause a decrease in gastric motility, responsible for the common side-effect of nausea, which tends to subside with time. GLP-1 analogs resulted in weight loss and had more gastrointestinal side-effects, while in general dipeptidyl peptidase-4 DPP-4 inhibitors were weight-neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs.

DPP-4 inhibitors increase blood concentration of the incretin GLP-1 by inhibiting its degradation by DPP DPP-4 inhibitors lowered hemoglobin A1C values by 0. A result in one RCT comprising patients aged 65 or older mean baseline HgbA1c of 7. Amylin agonist analogues slow gastric emptying and suppress glucagon.

They have all the incretins actions except stimulation of insulin secretion. As of [update] , pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea , which occurs mostly at the beginning of treatment and gradually reduces.

Typical reductions in A1C values are 0. SGLT2 inhibitors block the sodium-glucose linked transporter 2 proteins in renal tubules of nephrons in kidneys, reabsorption of glucose in into the renal tubules, promoting excretion of glucose in the urine.

This causes both mild weight loss, and a mild reduction in blood sugar levels with little risk of hypoglycemia. They may be considered first line in diabetic patients with cardiovascular disease, especially heart failure , as these medications have been shown to reduce the risk of hospitalization in patients with such comorbidities.

Furthermore, there has been growing evidence that the effectiveness and safety of this drug class could depend on genetic variability of the patients. The side effects of SGLT2 inhibitors are derived directly from their mechanism of action; these include an increased risk of: ketoacidosis , urinary tract infections , candidal vulvovaginitis , and hypoglycemia.

The following table compares some common anti-diabetic agents, generalizing classes, although there may be substantial variation in individual drugs of each class. When the table makes a comparison such as "lower risk" or "more convenient" the comparison is with the other drugs on the table.

Many anti-diabetes drugs are available as generics. These include: [49]. No generics are available for dipeptidyl peptidase-4 inhibitors Onglyza , the glifozins, the incretins and various combinations. Sitagliptin patent expired in July , leading to launch of generic sitagliptin [50] brands.

This lowered the cost of therapy for type 2 diabetes using sitagliptin. The effect of Ayurvedic treatments has been researched, however due to methodological flaws of relevant studies and research, it has not been possible to draw conclusions regarding efficacy of these treatments and there is insufficient evidence to recommend them.

Contents move to sidebar hide. Article Talk. Metformin lowers blood glucose levels primarily by decreasing the amount of glucose produced by the liver. Metformin also helps lower blood glucose levels by making muscle tissue more sensitive to insulin so blood glucose can be used for energy.

It is usually taken two times a day. A side effect of metformin may be diarrhea, but this is improved when the drug is taken with food.

DPP-4 inhibitors help improve A1C a measure of average blood glucose levels over two to three months without causing hypoglycemia low blood glucose. They work by preventing the breakdown of naturally occurring hormones in the body, GLP-1 and GIP.

These hormones reduce blood glucose levels in the body, but they are broken down very quickly so it does not work well when injected as a drug itself. By interfering in the process that breaks down GLP-1 and GIP, DPP-4 inhibitors allow these hormones to remain active in the body longer, lowering blood glucose levels only when they are elevated.

DPP-4 inhibitors do not cause weight gain and are usually very well tolerated. As noted in the description for DPP-4 inhibitors, GLP-1 and GIP are natural hormones in the body that help maintain glucose levels. These medications have similar effects to the GLP-1 and GIP produced in the body but are resistant to being broken down by the DPP-4 enzyme.

These medications can result in large benefits on lowering blood glucose and body weight. Some agents in this class have also been shown to prevent heart disease. Most of these medications are injected, with the exception of one that is taken by mouth once daily, called semaglutide Rybelsus.

How often you need to inject these medications varies from twice daily to once weekly, depending on the medication. The most common side effect with these medications is nausea and vomiting, which is more common when starting or increasing the dose.

Glucose in the bloodstream passes through the kidneys where it can either be excreted in the urine or reabsorbed back into the blood. Sodium-glucose cotransporter 2 SGLT2 works in the kidney to reabsorb glucose.

A new class of medication, SGLT2 inhibitors, block this action, causing excess glucose to be eliminated in the urine. By increasing the amount of glucose excreted in the urine, people can see improved blood glucose, some weight loss, and small decreases in blood pressure.

Bexagliflozin Brenzavvy , canagliflozin Invokana , dapagliflozin Farxiga , and empagliflozin Jardiance are SGLT2 inhibitors that have been approved by the Food and Drug Administration FDA to treat type 2 diabetes.

SGLT2 inhibitors are also known to help improve outcomes in people with heart disease, kidney disease, and heart failure. For this reason, these medications are often used in people with type 2 diabetes who also have heart or kidney problems. Because they increase glucose levels in the urine, the most common side effects include genital yeast infections.