Ozempic is one of the three formulations of Semaglutide, a novel GLP-1 agonist. The other two are:
- Rybelsus Tablets and
- Wegovy Injection
Ozempic is available as an injection that is administered once a week. Wegovy is also a once-weekly injection formulation of Semaglutide but a higher dose is administered.
Ozempic and Rybelsus are used to treat patients with Diabetes while Wegovy is approved for the treatment of Obesity.
The following overview is a summarized form of the FDA prescribing information [Ref]
Indications and Uses of Ozempic:
Ozempic is used to treat:
- Individuals with diabetes type 2 who are not well-controlled with diet, exercise, and/ or metformin. It is indicated for optimal glucose control in these patients.
- To reduce the risks of major adverse cardiovascular events in patients with diabetes type 2 and cardiovascular disease. Major adverse cardiovascular events include:
- Death from a cardiovascular cause
- Non-fatal Myocardial infarction
- Non-fatal stroke.
Ozempic should not be used to treat diabetes in the following situations:
- Individuals with diabetes mellitus type 1
- Individuals who have acute diabetes-related complications like Diabetic ketoacidosis and HHS (hyperosmolar hyperglycemic state)
- Individuals with pancreatitis or a past history of pancreatitis.
Ozempic Dose for Diabetes:
Ozempic injection is available as pre-filled pens that contain a total dose of 2 mg per pen. It is administered in a dose of:
- 0.25 mg subcutaneously every week for four weeks, followed by 0.5 mg every week. The dose can be increased to the maximum dose of 1 mg per week.
- Very recently, the maximum dose of Ozempic has been increased from 1 mg to 2 mg per week. This dose is close to the one used for weight loss (i.e. 2.4 mg per week).
Unlike Wegovy’s 2.4 mg per week injection, the dose of Ozempic should not exceed 1 mg per week.
One pen has a total dose of 2 mg. Thus, the first pen will last for six weeks (0.25 x4 +0.5 mg x 2 = 2 mg).
After the first four weeks, when the priming dosing of Ozempic is over, the next pen will last for four weeks. (Patients on 1 mg per week dose may need two pens of 1 mg each).
It is recommended to switch to 0.5 mg after the first four weeks as a 0.25 mg dose is just the treatment initiation dose. It is not recommended for optimal glucose control.
Secondly, the shelf half-life of Ozempic injection is six weeks maximum. After six weeks, the pen should be discarded. So, a person using 0.25 mg beyond the first four weeks has to discard the pen after a total dose of 1.5 mg has been administered (0.25 mg x 6 = 1.50 mg).
If you want to change your Ozempic dosing schedule …
If you want to change your schedule of Ozempic injection, you can switch to another day as per your ease, however, the time between two doses should be kept to a minimum of 48 hours (two days).
If you miss your dose, …
If you miss your dose of Ozempic, you can administer it as soon as possible and within five days of the last scheduled dose.
However, if more than five days have passed, skip that dose and administer the dose on the next scheduled day.
For example, you inject Ozempic every Sunday. Now, you missed this Sunday’s dose. You can administer it as soon as you remember before Friday.
If you remember on Friday or Saturday that you have missed your dose, you should skip it and administer your next dose on your scheduled day (Sunday).
The schedule of once-weekly Ozempic injections will resume thereafter.
How do you administer Ozempic Injections?
Ozempic injections are administered once a week into the skin of:
- Belly (3 to 5 cm away from the umbilicus)
- Thighs, and
- Upper arms
The injection site should be repeated every time. Furthermore, before the injection, inspect its contents. If the solution is cloudy, opaque, or discolored, it should not be used.
If you are on concomitant insulin as well, you can inject it keeping a little distance between the two injections. Preferably, you should inject Ozempic on one side and insulin on the other side of the abdomen, arm, or thighs.
Ozempic Contraindications and Warnings:
Ozempic use should be avoided in the following patients:
- Individuals who are allergic to the drug or any component of the injection
- Individuals with a personal or a family history of Medullary Thyroid Cancer or MEN-2 (multiple endocrine neoplasia type-2)
A detailed article on the association between Thyroid Cancer and Ozempic has already been published. You can view the article here:
Pancreatitis is a side effect of all GLP-1 analogs. It can manifest as new onset of abdominal pain that radiates to the back. It is usually accompanied by nausea and anorexia with or without vomiting.
Patients who develop pancreatitis should immediately discontinue the treatment. Supportive treatment should be initiated such as intravenous fluids, avoiding fatty meals, triggers that can cause pancreatitis, and medications for pain relief and vomiting.
Patients who have had a history of pancreatitis secondary to Ozempic or another formulation of Semaglutide should not be restarted on any of the formulations of Semaglutide.
Ozempic use has been associated with an increased incidence of diabetic retinopathy. In clinical trials, the incidence of diabetic retinopathy was 3% in patients using Ozempic compared to 1.8% in the placebo group.
Retinopathy has been observed with insulin and other diabetes medicines as well. It is thought to occur as a result of the rapid improvement in blood glucose.
Furthermore, the risk of worsening diabetic retinopathy is greater in patients with a background disease. With Ozempic it was 8.2% compared to 5.2% in the placebo group.
In patients without a history of diabetic retinopathy, the risk of diabetic retinopathy was 0.7% in the Ozempic-treated patients vs 0.4% in the placebo-treated patients.
It is recommended to monitor patients for diabetic retinopathy if they develop blurring or new-onset of eye-related symptoms.
Ozempic pen should not be shared by two individuals even if the needle is changed. There is a risk of infection transmission from one person to another.
Semaglutide does not cause hypoglycemia. However, in diabetic patients using insulin or insulin secretagogues like sulfonylureas, the risk of hypoglycemia is increased.
When starting Ozempic therapy, it is recommended to reduce the dose of insulin and sulfonylureas.
Acute renal failure:
Semaglutide use has caused patients to develop acute renal failure. In clinical trials, renal failure was seen commonly in those patients who had abnormal renal functions at baseline.
More often renal failure developed in patients with more severe gastrointestinal side effects such as nausea, vomiting, and dehydration.
However, new onset of kidney dysfunction was also observed.
Individuals who initiate treatment using Semaglutide should be monitored for worsening renal functions. Treatment should be discontinued if renal failure is observed.
Semaglutide, like other GLP-1 analogs, may cause serious allergic reactions. Patients have been reported to develop angioedema and anaphylaxis.
Those with a previous history of anaphylaxis or serious allergic reactions to Ozempic or other GLP-1 should not be advised to use the drug.
In case of any reaction, supportive care should be promptly initiated. Patients may be given intravenous fluids, antihistamines, corticosteroids, and/or epinephrine.
Ozempic Side effects:
The most common side effects of Semaglutide injection are related to the gastrointestinal tract. These included nausea, vomiting, diarrhea, constipation, and abdominal pain.
The relative percentage of these side effects is summarized in the table below:
|Commonly reported adverse reactions of Ozempic compared to placebo|
|Side effects||Placebo (262)||Ozempic 0.5 mg (260)||Ozempic 1 mg (261)|
Other gastrointestinal side effects that were more common in patients using Ozempic compared to placebo include:
- GERD (gastroesophageal reflux disease)
- Abdominal gases, and
Hypoglycemia is a common side effect of most anti-diabetic drugs. In clinical trials, there were no cases of severe hypoglycemia reported.
However, patients treated with 0.5 mg and 1 mg develop symptomatic hypoglycemia with blood glucose levels of 70 mg/dl or less in 1.6% and 3.8% of the patients respectively.
When Ozempic was used as an add-on therapy to insulin with or without metformin, the risk of hypoglycemia was more marked.
The percentage of the hypoglycemic episodes in patients using Ozempic 0.5 mg and 1 mg weekly compared to placebo is given in the table below:
Ozempic as an add-on treatment to insulin with or without metformin
|30 weeks||Placebo (132)||Ozempic 0.5 mg (132)||Ozempic 1 mg (131)|
|Severe hypoglycemia (=/<56 mg/dl)||5.3%||8.3%||10.7%|
|Symptomatic Hypoglycemia (=/<70 mg/dl)||15.2%||16.7%||29.8%|
In clinical trials, the overall incidence of gallstones was 1.5% and 0.4% in patients treated with Ozempic 0.5 mg and 1 mg respectively. There were no cases reported in patients treated with a placebo.
Effect of Semaglutide on Serum Amylase and Lipase levels:
In clinical trials, Semaglutide resulted in elevated levels of amylase and lipase in the blood. Serum amylase levels were elevated by 13% from the baseline. Serum Lipase levels were elevated by up to 22% from the baseline.
Patients treated with a placebo medicine did not have a change in their amylase and lipase levels.
- Injection site reactions can occur with Ozempic. The risk in clinical trials has been reported to be about 0.2% compared to placebo.
Fatigue, Altered taste, and dizziness:
- Fatigue is commonly reported in post-marketing studies, however, in clinical trials, the risk was estimated to be around 0.4%
- Similarly, altered taste and dizziness were also reported in a similar number of patients.
Effect on heart rate:
- Semaglutide use has been associated with an increase in heart rate. There is an average of 2 to 3 beats increase in patients who use Semaglutide compared to placebo.
Ozempic Drug Interactions:
Semaglutide does not have any effects on drug transporter proteins. It does not have any effect on either CYP enzyme induction or enzyme inhibition.
However, Semaglutide causes delayed gastric emptying that may impair the absorption of certain drugs including:
- Ethinylestradiol, and
The manufacturer, however, does not recommend any dose adjustments when combining these drugs with Semaglutide.
Ozempic Use in Pregnancy and Breastfeeding:
Semaglutide has not been studied in human pregnancies. However, in animal studies, it has resulted in structural defects, alterations in growth, and fetal deaths.
The risks of fetal malformations are also great in pregnant diabetic females who have uncontrolled diabetes.
Because uncontrolled diabetes during pregnancy and Semaglutide use may both have harmful effects on the developing fetus, the manufacturer recommends using an alternative treatment such as insulin.
Ozempic use during breastfeeding:
Semaglutide use in lactating mothers has not been studied. In animals, the drug was found in the milk of lactating animals, however, it has not been studied in humans.
The manufacturer recommends weighing the benefits and risks of Semaglutide and breastfeeding before treatment initiation or continuation.
Males and females of reproductive potential:
Semaglutide should be discontinued at least two months before a planned pregnancy because of its long half-life.
Ozempic use in children and older individuals:
Semaglutide has not been studied in individuals younger than 18 years of age. The manufacturer does not recommend its use in individuals less than 18 years of age.
Older individuals (75 years of age or more) may be sensitive to the drug. The incidence of side effects including hypoglycemia (especially when concomitant insulin or sulfonylureas are being used) may be greater in the older population.
In clinical trials, there was no difference in the safety or efficacy of Semaglutide in younger and older individuals, however, it should be used with caution.
Ozempic use in patients with kidney diseases:
Semaglutide has been studied in patients with mild, moderate, severe, and ESRD (end-stage renal disease). Kidney disease does not affect the pharmacokinetics of Semaglutide.
Hence, dose adjustment in patients with kidney disease has not been recommended by the manufacturer.
Ozempic use in patients with liver diseases:
Semaglutide has been studied in varying degrees of liver disease. Liver disease does not affect the pharmacokinetics of Semaglutide.
Hence, dose adjustment has not been recommended by the manufacturer in patients with liver disease.
What to do if you overdose on Ozempic?
Ozempic overdose can happen. However, as Ozempic is the low-dose formulation of Semaglutide, overdose is less likely.
Wegovy is Semaglutide administered in a dose of 2.4 mg weekly for weight loss. So, even if the maximum dose of Ozempic (1 mg) is doubled, it is still less than the dose of Wegovy.
However, a sudden increase in the dose can result in more side effects. The initial side effects are mostly related to the gastrointestinal tract. These include:
- Abdominal Pain
- Diarrhea, or Constipation
- Altered taste.
- Abdominal fullness.
Other serious side effects of Ozempic overdose may include pancreatitis, renal failure, and hypoglycemia.
In any case, it is better to consult your healthcare provider. Treatment is usually supportive by adhering to a healthy diet, keeping yourself well-hydrated, and antacids.
Ozempic MOA (Mechanism of action) and Pharmacology:
Ozempic is a GLP-1 agonist. It binds to the endogenous GLP-1 receptors and activates them. Semaglutide is 94% identical to the natural GLP-1.
Since Semaglutide binds to albumin when administered, it does not get cleared by the kidneys easily.
The binding of Semaglutide to albumin also prevents its degradation by the natural metabolic pathways (by the DPP-IV enzyme). This results in a very long half-life.
Semaglutide enhances the secretion of insulin and lowers glucagon levels. These effects of Semaglutide are greatest when the blood glucose is high. Thus, Semaglutide lowers blood glucose in a glucose-dependent mechanism.
Semaglutide also inhibits or delays gastric emptying. This has a slight post-prandial glucose-lowering effect. However, this effect is primarily responsible for the weight loss effects.
The mean fasting, 2-hour postprandial glucose, and mean plasma glucose-lowering effects of Semaglutide 1 mg are given in the table below:
Blood Glucose-Lowering effects of Ozempic 1 mg at 12 weeks compared to placebo
|Fasting blood glucose||29 mg/dl (22%)|
|2-hours Pos-prandial blood glucose||74 mg/dl (36%)|
|Mean 24-hour plasma glucose||30 mg/dl (22%)|
Semaglutide lowers glucagon levels. The effect of Semaglutide on glucagon levels is given in the table below:
Blood Glucose-Lowering effects of Ozempic 1 mg at 12 weeks compared to placebo
|Fasting Glucagon levels||8%|
|Pos-prandial Glucagon levels||14 to 15%|
|Mean 24-hour plasma Glucagon levels||12%|
Semaglutide does not have any effect on QT-interval.
- Semaglutide reaches its maximum plasma concentrations after 1 to 3 days of administration.
- Semaglutide reaches its steady-state concentration in about 4 to 5 weeks
- It has a bioavailability of 89%
Binding to Albumin:
- Semaglutide is extensively bound to albumin. >99% of the drug is albumin-bound.
The elimination half-life of Semaglutide:
- The elimination half-life of Semaglutide is about one week. The drug can exert its effects for up to five weeks after the last dose of administration.
- Semaglutide is metabolized by proteolytic degradation and beta-oxidation of the fatty acid chains.
- It is excreted via feces and urine. About 3% of the drug is excreted as such in the urine.
How to administer Ozempic Injections:
Ozempic injection is administered subcutaneously just like insulin. However, it is not insulin and should not be used to replace insulin.
It is administered once a week on a fixed day. The first dose should be administered by a healthcare provider. Your healthcare provider should show you how to inject it.
It can be administered in the skin around the umbilicus (3 to 5 cms away from the umbilicus), thighs, or upper arm. The injection sites should be rotated each time.
It should not be mixed with insulin or any other medications. When administering the dose, the solution of the injection should be clear and transparent.
Ozempic Injection price:
Prices vary in different parts of the world. It is usually advised to patients whose insurance cover the cost. With an insurance cover, the cost can be as low as USD 10.
In other parts of the world, the cost is very variable. It is better to check at your local pharmacy. In addition, NOVO also provides a patient support program and delivers Ozempic at a reasonable price compared to most local pharmacies.
Ozempic Price in the United States:
Prices vary but the price of one 1.5 mg pen costs around 815 USD.
Ozempic Price in Canada:
A monthly dose of Ozempic costs around 1000 USD.
Ozempic Price in the UK:
Ozempic’s calculated cost per day is around £2.62 per day.
Ozempic Price in Australia:
Ozempic’s monthly cost is around 800 USD.