Last reviewed by Miljan Krcobic on September 4th, 2018.
What type of drug is Metformin
Metformin is a Generic name for a drug with antihyperglycemic properties that is used for treating non – insulin – dependent diabetes mellitus.
This drug can improve glucose levels in blood by decreasing the production of glucose in liver, decreasing intestinal absorption of glucose and increasing insulin-mediated glucose uptake.
Therapy with metformin may also decrease the risk of having a stroke, heart attack, or other diabetes-related complications. Metformin can induce weight loss and that’s why it is the drug of choice for obese patients with diabetes type two.
When it is used alone, this drug doesn’t cause hypoglycemia as side effect; but, it may potentiate the hypoglycemic effects of sulfonylureas drugs and insulin if they are used together. Metformin is available in the form of tablet in following dosage forms: 500, 750, 850 and 1000 mg. It is usually taken during meals.
Common Brand names on the market containing metformin as an active ingredient are: Glucophage, Glumetza, Glucophage XR, Fortamet, Metformin Sandoz, Diabex, Diaformin, Siofor, Metfogamma and Riomet.
What is Januvia
Januvia is a Brand name for a drug containing sitagliptin as an active ingredient. It is an oral diabetes drug that is used to control sugar levels in blood. Januvia works by regulating insulin levels that body produces after eating.
This drug is used for the treatment of patints with type 2 diabetes. Januvia can be used in combination with other diabetes medicines, but is not used for treating type 1- diabetes.
Patients with diabetic ketoacidosis should not use Januvia. Januvia is available in tablet and film-coated tablet form in following strenghts: 25, 50 and 100 mg.
Common Brand names on the market containing sitagliptin as an active ingredient are: Xelevia and Janumet.
How does Metformin and Januvia work in the body
Metformin reduces glucose levels in blood by decreasing the hepatic glucose production and intestinal glucose absorption, and by improving cell sensitivity to insulin by increasing peripheral uptake of glucose and utilization.
These effects are mediated by the initial activation of AMP-activated protein kinase which is a liver enzyme that plays a significant role in insulin signalization, energy balance, and the metabolism of glucose and lipids.
Activation of AMP- protein kinase is needed for inhibitory effect of metformin on liver cell production. Increased peripheral utilization of glucose is caused by improved insulin binding to its receptors.
Metformin administration also increases AMP- protein kinase in skeletal muscle cells. AMP- protein kinase is known to cause deployment of GLUT-4 to the cell plasma membrane, which results in insulin-independent glucose uptake.
The rare side effect called lactic acidosis can be caused by decreased liver uptake of lactate, which is one of the substrates of gluconeogenesis. Patients who have healthy renal function, the slight excess are simply cleared.
However, patients who have severe renal impairment the accumulation of lactic acid can be clinically significant. Conditions such as severe hepatic disease and acute/decompensated heart failure may precipitate lactic acidosis.
Sitagliptin works by inhibiting enzyme called dipeptidyl peptidase-4 (DPP-4). In patients with type 2 diabetes it works by slowing the incretin hormones inactivation, thus increasing these hormones amount and prolonging their actions.
Incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). They are released by the intestine during the day and levels are increased in response to a meal.
These hormones are rapidly inactivated by the enzyme, DPP-4. When glucose concentrations in blood are normal or elevated, GIP and GLP-1 increase synthesis of insulin and its release from pancreatic beta cells through intracellular signaling pathways involving cyclic AMP.
GLP-1 can also lower secretion of glucagon from pancreatic alpha cells that lead to reduced production of glucose in the liver. These changes lead to a decrease in hemoglobin A1c (HbA1c) levels, as well as a lower fasting and postprandial glucose levels in blood.
The main benefit of this drug is reduced side-effects of hypoglycemia in the management of glucose levels in blood.
Can patients take Metformin and Januvia together
Metformin and sitagliptin are often prescribed together for the treatment of high blood sugar levels in patients with type 2 diabetes that can’t be controlled with metformin monotherapy.
They work through different mechanism but their effects are synergistic. Metformin reduces the absorption of glucose, reduces the release of stored glucose in the liver, and helps body to use glucose better while Januvia controls blood sugar by helping the pancreas to release more insulin and to lower the release of glucagon during meals.
Januvia doesn’t cause hypoglycemia, and that’s why this combination is considered to be safe. However, this combination doesn’t help patients who have insulin-dependent diabetes mellitus (type 1).
There is also product on the market called Janumet that already contain combination of metformin and sitagliptin in one tablet.
Patients should use these drugs together only if they are prescribed by the doctor. These drugs can cause serious side effects in patients with ketoacidosis and decreased renal function.
The table below shows side effects after Metformin and Januvia administration in recommendable doses. The incidence can be significantly increased if these drugs are overdosed or taken together.
|Frequency Not Defined||Asthenia, Diarrhea, Flatulence, Weakness, Myalgia, Upper respiratory tract infection, Hypoglycemia, GI complaints, Lactic acidosis (rare), Low serum vitamin B-12, Nausea/vomiting, Chest discomfort, Chills, Dizziness, Abdominal distention, Constipation, Heartburn, Dyspepsia, Nasopharyngitis, Headache, Peripheral edema, Pharyngitis, Osteoarthritis|
Special precautions and warnings during Metformin and Januvia administration:
- Before taking these medicines, patients should tell their doctor or pharmacist if they are allergic to Metformin or Januvia or if they have any other allergies. These products may contain inactive ingredients that can cause allergic reactions or other problems.
- Patients should tell their doctor and pharmacist what prescription and nonprescription medications, nutritional supplements, vitamins and herbal products they are taking or plan to take. Patients should mention any of the following drugs: digoxin, insulin, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, tolazamide and tolbutamide. Doctor may need to change the doses of these medications or monitor carefully for side effects.
- Before using Metformin, patients should tell their doctor or pharmacist their medical history, especially if they ever had or have: breathing problems such as obstructive lung disease and asthma, blood problems such as anemia or vitamin B12 deficiency, kidney or liver disease.
- Patients using Januvia should tell their doctor if they drink or have ever drunk large amounts of alcohol and if they have or ever had diabetic ketoacidosis, pancreatitis, gallstones, high levels of triglycerides in blood, or kidney disease.
- Patients should tell their doctor if they are pregnant, plan to become pregnant, or are breastfeeding. If they become pregnant while using Januvia or Metformin they should call a doctor. Pregnant patients should use Metformin only when it is clearly needed. Patients should discuss the risks and benefits with their doctor. Doctor may direct to use insulin instead of metformin during pregnancy.
- Patients should tell their doctors that they are using metformin before having surgery or any X-ray scanning procedure that use injectable iodinated contrast material.
- Patients may experience blurred vision, drowsiness or dizziness, or due to extremely low or high blood sugar levels. They should not drive, use machinery, or do any activity that requires alertness or clear vision until they are sure that they can perform such activities safely.
- Patients should limit the usage of alcohol while using these medications because alcohol can increase the risk of lactic acidosis and low blood sugar can be developed.
- High fever, diuretic such as hydrochlorothiazide, too much sweating, prolonged diarrhea, and vomiting may cause dehydration and increase the risk of lactic acidosis. Patients should stop taking metformin and tell their doctor if they have prolonged diarrhea or vomiting.
- Geriatric patients may be at higher risk for side effects such as low blood sugar or lactic acidosis.
- Metformin can make changes in the menstrual cycle, such as promote ovulation and this drug may also increase the risk of becoming pregnant.
- Metformin can pass into breast milk, but only in small amounts. Patients should consult their doctor before breast-feeding.
- Patients should talk with their doctor if they get hurt or develop a fever or infection. These conditions may affect blood sugar levels.
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