Types of Diabetes Type 2 Medications

9 Types of drug classes of diabetes type 2 oral medications.

Oral diabetes medications are used to improve blood sugar (glucose) control in patients with type 2 diabetes.

Currently, there are nine drug classes of oral diabetes medications approved for the treatment of type 2 diabetes.

1. α-glucosidase inhibitors
2. Biguanides
3. Sulfonylureas
4. Meglitinides
5. Thiazolidinediones
6. DPP-4 inhibitors
7. Sodium-glucose cotransporter (SGLT)-2 inhibitors
8. Dopamine agonists
9. Bile acid sequestrants

These medications differ in the way they function in the body to reduce blood glucose.

Biguanides

Metformin (Glucophage) is the only biguanide available in the United States and is generally the first choice for oral treatment of type 2 diabetes mellitus.

Metformin improves the following:

• The body's response to natural insulin
• Decreases the absorption of glucose from the intestines
• Reduces the production of glucose by the liver

Sulfonylureas

Sulfonylureas are the oldest class of oral diabetes medications. Sulfonylureas work primarily by stimulating the release of insulin. Insulin is the hormone responsible for regulating blood glucose by increasing the uptake of blood glucose by tissues and increasing the storage of glucose in the liver.

Meglitinides

Meglitinides and sulfonylureas have a similar mechanism of action. Meglitinides are short-acting glucose-lowering medications. They stimulate the secretion of insulin from the pancreas.

Thiazolidinediones

Thiazolidinediones enhance insulin sensitivity meaning that the effect of a given amount of insulin is greater. Thiazolidinediones also are referred to as peroxisome proliferator-activated receptor ? or PPAR-? agonists.

α-glucosidase inhibitors

α-glucosidase inhibitors delay the digestion and absorption of starch or carbohydrates by inhibiting enzymes in the small intestine which help break down these molecules. The starches and carbohydrates are broken down into glucose, which then is absorbed from the intestine and increases the level in the blood.

DPP-4 inhibitors

DPP-4 inhibitors help lower blood glucose by increasing the production of insulin from the pancreas and reducing the release of glucose from the liver.

SGLT2 inhibitors

SGLT2 inhibitors or sodium-glucose cotransporter 2 inhibitors are the newest class of oral diabetes medications. They work by reducing the absorption of glucose from the fluid that is filtered from the blood by the kidney, causing more glucose to be eliminated in the urine. These medications increase urinary glucose excretion and consequently lower blood sugar levels.

Bile acid sequestrants

Currently, the only bile acid sequestrant approved for the oral treatment of type 2 diabetes is colesevelam (Welchol). Bile acid sequestrants function primarily in the intestines where they bind to and decrease the reabsorption of bile acid. The exact mechanism by which these agents lower blood glucose is not known.

Dopamine agonists

Bromocriptine (Cycloset) is a dopamine agonist approved for the treatment of type 2 diabetes. The exact mechanism whereby bromocriptine lowers blood glucose is not known.

α-glucosidase inhibitors

• acarbose (Precose)
• miglitol (Glyset)

Sulfonylureas

Sulfonylureas are grouped into two classes, first and second-generation agents.

First-generation sulfonylureas include:

• acetohexamide (Dymelor)
• chlorpropamide (Diabinese)
• tolazamide (Tolinase)
• tolbutamide (Orinase)

Second-generation sulfonylureas are:

• glimepiride (Amaryl)
• glipizide (Glucotrol, Glucotrol XL)
• glyburide (DiaBeta, Micronase)

Biguanides

The only biguanide available in the United States is metformin (Glucophage, Glucophage XR, Riomet).

Thiazolidinediones

Thiazolidinediones or TZDs include:

• pioglitazone (Actos)
• rosiglitazone (Avandia)

Meglitinides

• nateglinide (Starlix) and repaglinide (Prandin)

DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors)

• sitagliptin (Januvia)
• saxagliptin (Onglyza)
• linagliptin (Tradjenta)
• alogliptin (Nesina)

SGLT-2 inhibitors

• empagliflozin (Jardiance)
• canagliflozin (Invokana)
• dapagliflozin (Farxiga)

Bile acid sequestrants

Currently, the only bile acid sequestrant approved for the oral treatment of type 2 diabetes is colesevelam (Welchol).

Dopamine agonists

Bromocriptine mesylate (Cycloset) is a dopamine agonist.

Combination oral diabetes drugs include:

• glyburide/metformin (Glucovance)
• glipizide/metformin (Metaglip)
• rosiglitazone/metformin (Avandamet)
• pioglitazone/metformin (Actoplus Met)
• pioglitazone/glimepiride (Duetact)
• alogliptin/metformin (Kazano)
• canagliflozin/metformin (Invokamet)
• dapagliflozin/ metformin (Xigduo XR)
• sitagliptin/ metformin (Janumet XR)
• saxagliptin/ metformin (Kombiglyze XR)
• linagliptin/ metformin (Jentadueto)
• repaglinide/metformin (PrandiMet)

The nine classes of oral diabetes drugs differ in their side effect profile. The main side effects of each class are as listed.

Thiazolidinediones may cause:

• Liver disease
• Fluid retention
• Weight gain
• Increased risk for fractures
• Increased risk for bladder cancer
• Increased risk for ovulation which may result in pregnancies

Although DPP-4 inhibitors are generally well tolerated, they may cause:

• Hypoglycemia
• Headache
• Nasopharyngitis
• Fluid retention
• Hives
• Urinary tract infections (UTIs)
• Facial swelling

The most common side effects of metformin include:

• Stomach discomfort
• Upset stomach
• Diarrhea
• Decreased appetite

These side effects usually are mild and tend to decrease in severity over time despite the continuation of treatment.

Other reported side effects of metformin include:

• Metallic taste
• Interference with vitamin B12 absorption
• Exercise-induced hypoglycemia

Although rare, metformin may cause lactic acidosis, a serious condition that occurs due to the accumulation of acid in the body.

Sulfonylureas most commonly cause hypoglycemia (low blood glucose) and weight gain.

Less common side effects include:

• Skin rash
• Drop in red blood cell count
• Liver disease
• Upset stomach

The most common side effects of meglitinides are hypoglycemia and weight gain. The risk for hypoglycemia and weight gain appears to be low in comparison to sulfonylureas.

α-glucosidase inhibitors most commonly cause the following:

• Gas
• Bloating
• Upset stomach
• Diarrhea

The most common side effects associated with SGLT-2 inhibitors include:

• Vaginal yeast infections
• Yeast infections of the penis
• Upper respiratory tract infections
• UTIs
• Changes in urination (urinary urgency, urinating more often and in larger amounts)

Other reported side effects include:

• Hypotension (decrease in blood pressure)
• Kidney dysfunction
• Dehydration
• Hypoglycemia when combined with insulin or drugs that increase insulin secretion
• Increase in cholesterol
• Bladder cancer
• Hypersensitivity reactions

The most common side effects of bile acid sequestrants include:

• Stomach discomfort or pain
• Constipation
• Heartburn

Colesevelam also may cause an increase in triglyceride levels.

Side effects associated with bromocriptine therapy include:

• Nausea
• Runny nose
• Headache
• Weakness
• Dizziness
• Constipation
• Sinusitis

Drug interactions with oral diabetes drugs vary based on individual diabetes drug classes. However, drugs that cause blood glucose levels to increase may diminish the effectiveness of any oral diabetes drug therapy.

Examples of drugs that increase blood glucose include:

• thiazide diuretics
• other diuretics
• corticosteroids,
• phenothiazines
• thyroid medications
• estrogens
• birth control pills
• phenytoin (Dilantin)
• nicotinic acid
• calcium channel blockers (CCBs)
• isoniazid (Nydrazid)

Metformin drug interactions

Metformin is eliminated from the body via the kidneys in a process known as renal tubular secretion. Drugs that are also eliminated via this same pathway may compete with metformin for elimination when administered concomitantly and increase the risk of metformin-associated side effects due to an increase in blood levels of metformin.

Examples of such drugs include

• amiloride (Midamor)
• digoxin (Lanoxin)
• morphine
• procainamide (Procanbid)
• quinidine (Quin-Tab)
• quinine (Qualaquin)
• ranitidine
• triamterene (Dyrenium)
• trimethoprim (Primsol)
• dofetilide (Tikosyn)
• vancomycin (Vancocin)

Due to the risk of lactic acidosis metformin-containing products must be temporarily discontinued before the administration of radiopaque contrast dyes. Metformin should be held for at least 48 hours after contrast dye administration and should not be restarted until the patient's kidney function returns to normal.

Other drug interactions with oral diabetes medications

• Sulfonylureas are broken down (metabolized) by a set of liver enzymes. Medications that inhibit or induce the activity of these enzymes may impact their blood levels.
• Gemfibrozil (Lopid) strongly inhibits the breakdown of repaglinide and consequently may cause prolonged hypoglycemia.
• Thiazolidinediones may interact with drugs that are strong inhibitors or inducers of liver certain enzymes known as CYP3A4, CYP2C8, or CYP2C9. The dose of pioglitazone must be limited to 15 mg when administered in combination with gemfibrozil (Lopid), a strong inhibitor of these pathways.
• DPP-4 inhibitors are metabolized extensively by liver enzymes. Therefore, drug-drug interactions are possible with agents that alter the function of these enzymes.
• The effectiveness of meglitinides may be reduced when administered with carbohydrate-digesting enzymes such as amylase, pancreatin, or pancrelipase.
• Bile acid sequestrants have many drug interactions. Bile acid sequestrants decrease the absorption of levothyroxine (Synthroid), glyburide (DiaBeta, Micronase), and birth control pills when administered together. Additionally, they may also decrease the absorption of other drugs such as warfarin (Coumadin), digoxin (Lanoxin), and fat-soluble vitamins (Vitamins A, D, E, and K). Therefore, these agents should be administered at least 4 hours before the dose of colesevelam.
• Bromocriptine is metabolized by CYP3A4 liver enzymes. Drugs that alter the activity of these enzymes may change bromocriptine levels in the blood and consequently cause adverse effects. Bromocriptine may also interact with some antipsychotics and ergot-based migraine medications.

• All oral diabetes drugs are available in tablet forms.
• Glipizide and metformin are available as extended-release tablets.
• Metformin also is available in an oral liquid form.
• Colesevelam is available as an oral powder for suspension.

The use of oral diabetes drugs during pregnancy is controversial. For most women, the first step to maintaining optimal blood glucose control during pregnancy is to make appropriate lifestyle and dietary changes. Insulin therapy is the preferred treatment of pregnant women with gestational diabetes or type 2 diabetes who fail to achieve adequate blood glucose control with dietary or lifestyle (for example, exercise, weight reduction) changes alone.

With the exception of glyburide, all sulfonylureas are classified as FDA pregnancy risk category C (risk not ruled out).

• Meglitinides, TZDs also are classified as FDA pregnancy risk category C.
• Glyburide, metformin, DPP-4 inhibitors, α-glucosidase inhibitors, colesevelam, and bromocriptine are categorized as pregnancy risk category B (no risk in animal studies).
• To prevent fetal harm, use of oral diabetes medications should be avoided during pregnancy if possible.

Oral diabetes drugs can enter the breast milk and can cause hypoglycemia in the newborn. Therefore, careful risk and benefit analysis should be made for each mother and her infant before a decision is made. Use of oral diabetes medications in nursing mothers should be avoided if possible.