Drug Detail:Semaglutide (Semaglutide)
Drug Class: Incretin mimetics
1. How it works
- Semaglutide may be given to treat type 2 diabetes and/or to reduce the risk of future cardiovascular events.
- Semaglutide works by mimicking the action of GLP-1, a naturally occurring hormone that helps to regulate blood glucose levels. By binding to and activating the GLP-1 receptor, it stimulates insulin secretion and lowers glucagon secretion when blood glucose levels are high. It also causes a slowing down in how fast the stomach empties.
- Semaglutide belongs to the class of medicines called GLP-1 receptor agonists.
2. Upsides
- May be used to improve blood sugar control (also called glycemic control) in people with type 2 diabetes alongside diet modification and increased exercise.
- Reduces the risk of future cardiovascular events, such as a heart attack or stroke, in people with type 2 diabetes who also have heart disease.
- May reduce the risk of new or worsening nephropathy in people with type 2 diabetes at high risk for or with existing cardiovascular disease.
- May be given alone or in combination with other antidiabetic agents such as metformin, insulin, or a sulfonylurea. Early initiation of combination treatment is encouraged because it helps to more rapidly establish good blood glucose control and prolongs the time to treatment failure.
- Effective at reducing blood glucose levels and it also reduces body weight.
- Available orally as 3mg, 7mg, and 14mg tablets (Rybelsus brand). Also available as a once-weekly prefilled injection pen that is given subcutaneously (under the skin) (Ozempic brand). The injection is given once a week, on the same day each week (for example, every Monday).
- The Wegovy brand of semaglutide is also approved in addition to diet and exercise to help reduce weight in obese or overweight adults.
- The dosage of semaglutide does not need to be adjusted in people with kidney or liver disease.
3. Downsides
If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:
- Hypoglycemia (low blood sugar levels), nausea, vomiting, diarrhea, abdominal pain, and constipation are commonly reported side effects.
- Given orally or by injection under the skin (subcutaneously), once a week. Self-administration of the prefilled pen injection is easy to learn for most people.
- Not considered as first-line therapy for type 2 diabetes.
- Semaglutide does not take the place of insulin and is not effective in people with type 1 diabetes or for the treatment of diabetic ketoacidosis.
- Animal studies have reported thyroid C-cell tumors in rats given semaglutide. It is not known if semaglutide increases the risk of these tumors in humans.
- Should not be used in people with a history of thyroid cancer or those with Multiple Endocrine Neoplasia syndrome type 2 or a family history of this condition. The value of monitoring serum calcitonin or the use of thyroid ultrasound for early detection of MTC is not certain.
- May increase the risk of pancreatitis. If this occurs, semaglutide should be discontinued and not restarted. There have also been reports of kidney damage, which may require hemodialysis, in people treated with GLP-1 receptor agonists (RA), such as semaglutide. Anaphylaxis and angioedema have also been reported with GLP-1 RAs and the initial administration of semaglutide should preferably be done in a medical facility.
- Has not been adequately studied in pregnant women and should not be used unless the perceived benefits outweigh the risks of uncontrolled diabetes, which include preeclampsia, spontaneous abortions, and preterm delivery.
Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects
4. Tips
- Take oral semaglutide once a day with a small glass of water (no more than 120mL) at least 30 minutes before the first food, beverage, or other oral drugs of the day. Swallow the tablets whole, do not cut, crush, or chew. If you miss a dose, omit the missed dose and just take the next dose the following day.
- If you are prescribed a semaglutide prefilled injection pen, ask your doctor or nurse to show you how to self-administer it before you do it yourself. Semaglutide should be injected just under the skin into the abdomen, thigh, or upper arm. Change injection sites each week so that you are not injecting into the same bit of skin every week. Always inspect the injection and do not use the injection if it contains particles or discoloration is seen.
- If you also need to self-administer insulin, administer the insulin at a different site to semaglutide, at least 15cm apart. Never mix insulin with semaglutide and never share your injection with another person. Taking semaglutide with insulin (as well as other medications such as sulfonylureas that also lower blood sugar levels) increases your risk of hypoglycemia (low blood sugar levels) so monitor yourself for symptoms of low blood sugar which include sweating, shaking, dizziness, a fast heartbeat, and mood changes.
- If you need to change the day you administer semaglutide, you can, as long as you allow at least 48 hours between two doses (for example, you can change from a Monday administration to a Wednesday administration).
- If you miss your injection of semaglutide, administer it as soon as possible, but within 5 days of the missed dose. If more than five days have passed, skip the missed dose and just administer the next dose on the regularly scheduled day.
- Report any symptoms of a possible thyroid tumor (such as a lump in the neck, shortness of breath, difficulty swallowing, or persistent hoarseness) to your doctor immediately.
- If you develop persistent, severe, abdominal pain, which may radiate to the back or be accompanied by vomiting, ring your doctor immediately as semaglutide can increase your risk of developing pancreatitis.
- Semaglutide may temporarily worsen diabetic retinopathy, an eye condition. Tell your doctor if you notice any change in your vision. If you are a woman, use adequate contraception to ensure you do not become pregnant while taking semaglutide. For a planned pregnancy, it is recommended semaglutide is discontinued at least two months before conception. Tell your doctor if you inadvertently become pregnant while taking semaglutide.
5. Response and effectiveness
- Treatment with semaglutide 1mg subcutaneously reduced blood glucose levels by 22% when fasting, 36% two hours after eating a meal, and 22% over 24 hours.
- Insulin secretion typically occurs in two phases following a meal, and semaglutide increased both first and second phase insulin secretion.
- Semaglutide also reduced glucagon release by the liver by 8% (fasting), 14-15% after a meal, and 12% over 24 hours.
- After Semaglutide administration the insulin secretion rate in people with type 2 diabetes was similar to that of healthy people.
- Taking oral semaglutide less than 30 minutes before food, beverages, or other oral drugs will lessen its effects.
6. Interactions
Medicines that interact with semaglutide may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with semaglutide. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.
Common medications that may interact with semaglutide include:
- acetazolamide
- anticonvulsants such as phenytoin
- antidepressants such as tricyclic antidepressants (such as amitriptyline, nortriptyline) or monoamine oxidase inhibitors (MAOI) (eg, selegiline, isocarboxazid, and phenelzine)
- antipsychotics, such as aripiprazole
- beta-blockers, such as atenolol, labetalol, and metoprolol, may enhance the hypoglycemic effects
- bexarotene
- ciprofloxacin
- corticosteroids, such as prednisone or cortisone
- diuretics, such as bumetanide, HCTZ, and bendroflumethiazide
- HIV medications, such as amprenavir, atazanavir, and fosamprenavir
- hormones, such as ethinylestradiol and hydroxyprogesterone
- insulin (may increase risk of hypoglycemia)
- isoniazid
- other medications that affect blood sugar levels or are used for diabetes, such as glimepiride, or metformin.
Semaglutide may also enhance the toxic effects of alcohol, causing flushing.
Note that this list is not all-inclusive and includes only common medications that may interact with semaglutide. You should refer to the prescribing information for semaglutide for a complete list of interactions.
Also, because semaglutide causes a delay in gastric emptying, it may impact the absorption of any medication taken orally. However, in clinical trials, this did not appear to change the effects of other medications.