- Alpha-glucosidase inhibitors: Acarbose and miglitol are drugs that belong to a group called alpha glucosidase inhibitors. They inhibit the enzyme alpha glucosidase in the small intestine, which helps in the digestion of complex carbohydrates like starch. Thus, they delay the digestion of the complex carbohydrates thereby reducing the amount of glucose absorbed and the postprandial blood glucose level. They are administered just before each meal. Since they act on the gastrointestinal tract, side effects are also related to gastrointestinal function and include abdominal pain, diarrhea and flatulence, which reduce with further treatment. Hypoglycemia can occur when they are administered along with sulfonylureas; this hypoglycemia should be treated with glucose and not sugar. These drugs should not be used in patients with inflammatory bowel disease or kidney disease. Acarbose should also be avoided in those with liver disease.
- Colesevelam hydrochloride: Colesevelam hydrochloride is a drug that is used as an additional therapy for patients who are not controlled adequately on other diabetes medications. It may reduce the absorption of glucose, though its exact mechanism of action is not known. Once taken orally, it remains in the digestive tract and is not absorbed into the blood. Side effects are mainly gastrointestinal like flatulence, diarrhea and indigestion. It should not be taken at the same time as other medications since it may prevent their absorption. It should also not be used in patients with digestive tract disorders, pancreatitis and hypertriglyceridemia.
- Dipeptidyl peptidase-4 inhibitors: A relatively newer group of drugs, sitagliptin, saxagliptin, linagliptin and alogliptin act by inhibiting an enzyme called dipeptidyl peptidase-4 (DDP-4).
The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) decrease glucagon level and increase insulin secretion. Thus, they reduce blood sugar. Incretins are normally destroyed by the enzyme dipeptidyl peptidase-4 (DDP-4). Thus, by inhibiting this enzyme with medications, the blood level of incretins increases and the blood sugar is reduced.
Side effects include upper respiratory tract infection and inflammation, headache, hypoglycemia when combined with certain other diabetes medications, pancreatitis and allergic reactions. A newer drug vildagliptin is available in some countries.
- Selective sodium-glucose transporter-2 (SGLT-2) inhibitors: The SGLT-2 inhibitors act at the level of the kidney. They allow excessive glucose to be excreted via the urine. However, this action is seen only when the blood glucose rises above normal; they do not reduce the blood glucose levels below normal. Drugs in this group include canagliflozin, dapagliflozin and empagliflozin. The FDA has recently issued a warning that these drugs can cause a serious condition called diabetic ketoacidosis, which requires emergency treatment. Other possible adverse effects include dehydration, kidney problems, hypoglycemia when combined with other medications to treat diabetes, high cholesterol levels, and fungal infections in the urogenital tract due to increased urinary glucose concentration.
Besides the oral antidiabetes drugs and insulin, there are some other drugs that are administered as injection. These include the amylin analogue pramlintide, and the glucagon-like polypeptide-1 (GLP-1) receptor agonists, exenatide and liraglutide.
- Pramlintide: Pramlintide is an analogue of amylin, another hormone secreted but the pancreas. It acts via several mechanisms like reducing glucagon release, delaying gastric emptying and reducing appetite. Pramlintide is not an oral hypoglycemic agent per se, since is given in diabetes patients as an injection in the abdomen or thigh. It is given along with insulin in a separate syringe just before meals.
Side effects include hypoglycemia, anorexia, nausea and vomiting.
- Glucagon-like polypeptide-1 (GLP-1) receptor agonists: The GLP-1 receptor agonists include the drugs exenatide, albiglutide, liraglutide and dulaglutide. These drugs increase insulin secretion in response to high glucose levels in the body, reduce glucagon secretion after a meal, slow gastric emptying and reduce appetite. Exanatide is administered as an injection an hour before meals. Liraglutide is long acting and can be administered once a day.
Side effects include headache, nausea, diarrhoea, hypoglycemia when given with sulfonylureas, and pancreatitis. These medications should not be given to patients taking insulin. These drugs should not be given to patients with a history of thyroid cancer or multiple endocrine neoplasia type 2, or with a family history of the same.
Albiglutide and dulaglutide can be administered once a week.
In addition to the above drugs, the drug bromocriptine has also been approved for the treatment of type 2 diabetes since it plays a role in maintaining blood glucose level.
Treatment for type 2 diabetes is usually started with an older agent. The older drugs have been time tested. Newer drugs are often added to the older drugs to bring about better control in those who do not respond completely. Some newer drugs are associated with side effects. Since diabetes is a life-long disease, unless further information is available about their long-term safety, these drugs will not be preferred as the initial agents.
The most common drug to begin treatment is metformin. The dose is increased till the required glucose level is achieved. If the required glucose level is not achieved or if the patient develops side effects to the higher dose, a second drug is added.
Why are Combination Drugs Used?
Combination of drugs in diabetes is sometimes necessary. Drugs that act by different mechanisms can bring about an additional effect. Thus, the combination can help control blood glucose levels in those whose blood sugar cannot be controlled with a single medication.
Why use Insulin with Drugs?
Patients who do not achieve good control of blood sugar despite taking multiple oral antidiabetic drugs are prescribed insulin for additional effect. Initially, the insulin is administered at bedtime. If control is still not achieved, the patient should be shifted to regular insulin therapy.
Insulin is also used to replace the oral hypoglycemic drugs in emergency conditions like surgery or severe infections.
Important Health Tips for Diabetes
- The importance of diet control and exercise in a diabetes patient should not be underestimated. Even if you are taking antidiabetes medications, these measures will help to keep your dose at the minimum.
- Get yourself a regular check-up for complications of diabetes. If they can be controlled in the early stages, you may be able to avoid disability due to diabetes.
- If you feel your medications are causing low blood sugar, do not hesitate to take glucose. An urgent visit to your health care provider should be fixed to monitor your blood glucose levels and adjust your medication intake.
