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Exploring the Efficacy and Safety of Once-Weekly Semaglutide

Comparing Daily vs. Once-Weekly Semaglutide: What You Need to Know

Semaglutide is a promising new medication for managing type 2 diabetes. It is a glucagon-like peptide-1 (GLP-1) receptor agonist that helps lower blood sugar levels by stimulating insulin release and suppressing glucagon secretion.

Semaglutide is available in two formulations: a once-daily oral tablet (Rybelsus) and a once-weekly subcutaneous injection (Ozempic, Wegovy). In this article, we'll focus specifically on the efficacy and safety of the once-weekly injectable semaglutide for treating type 2 diabetes.

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Overview of Once-Weekly Semaglutide

Once-weekly semaglutide is administered as a subcutaneous injection under the skin using a pre-filled pen device.

It is available in three dose strengths - 0.5 mg, 1 mg, and 2 mg. Treatment usually starts with 0.25 mg for 4 weeks, then increases to 0.5 mg, with further adjustments based on glycemic response and tolerability.

Semaglutide mimics the effects of endogenous GLP-1, which helps regulate blood glucose by stimulating insulin and suppressing glucagon in a glucose-dependent manner. This means it lowers high blood sugar levels while minimizing the risk of hypoglycemia.

Weekly vs Daily Dosing of Semaglutide

The biggest advantage of weekly dosing is the convenience and ease of administration compared to taking a daily tablet.

With just one injection per week, it promotes better adherence. Since it provides a steady level of the drug, it also results in more consistent glycemic control.

However, the weekly injection causes a delayed rise and fall in semaglutide concentrations. With daily dosing, the drug effect aligns more closely with daily activities like meals.

A meta-analysis found that both weekly and daily semaglutide effectively lower HbA1c and fasting glucose levels in patients with type 2 diabetes, with only minor differences in efficacy.

So, How Do the Two Formulations of Semaglutide Compare?

Both once-weekly injectable and once-daily oral semaglutide are effective options for managing type 2 diabetes.

Some key differences:

  • The injectable leads to slightly better blood glucose reductions, while the oral form offers greater convenience.
  • Gastrointestinal side effects are more common with oral semaglutide.
  • Oral semaglutide has lower bioavailability and greater inter- and intra- patient variability.
  • The injectable form is approved for both diabetes and weight management, while the oral tablet currently has diabetes-only indications.

Overall, the efficacy and safety profiles of both formulations are comparable. Treatment decisions can be individualized based on patient preferences and needs.

Effectiveness of Semaglutide in Diabetes Management

Semaglutide has been extensively studied in the SUSTAIN phase 3 clinical trial program which demonstrated its efficacy and safety.

Some key findings on its effectiveness:

  • Once-weekly semaglutide (0.5 mg and 1 mg) resulted in significant reductions in HbA1c compared to placebo and sitagliptin.
  • It was non-inferior to once-daily liraglutide (another GLP-1 receptor agonist) in lowering HbA1c.
  • Addition of semaglutide to 1-2 oral anti-diabetic drugs led to better glycemic control vs placebo.
  • Combination with insulin also improved glycemic control significantly more than placebo.

Based on its positive impact on glycemic markers, semaglutide helps achieve diabetes treatment goals and reduces complications.

Effectiveness in Weight Loss

efficacy and safety of onceweekly semaglutide

Along with lowering blood glucose, semaglutide also promotes weight loss which further improves diabetes outcomes.

In the SUSTAIN studies, patients on semaglutide had significantly greater weight reduction compared to placebo and active comparators. This weight loss was sustained over 2 years.

At the 2.4 mg dose, semaglutide led to an average weight loss of 6.5% over 68 weeks.

How to Administer Weekly Injectable Semaglutide

Semaglutide comes in a pre-filled, multi-dose pen that makes self-injection simple and convenient.

Here are some tips on how to administer it correctly:

  • Start with proper hand hygiene and cleaning of the injection site with an alcohol pad.
  • Use the injection pen to select the appropriate dose as prescribed by your doctor.
  • Pinch the skin of your abdomen, thigh, or upper arm and insert the needle at 90°. Press the dose button until the display shows 0.
  • Hold for 6 seconds before removing the needle. Discard used needles safely.
  • Rotate sites every week - abdomen, thighs, back of arms are all options.
  • Inject on the same day, at any time of day, with or without meals.

What to Do If You Miss a Dose

Missed Dose Guidelines for Oral Semaglutide (Rybelsus):

  • Action on Missed Dose: If you miss a dose, do not take the missed dose. Continue with your next dose at the regular scheduled time.
  • Important Note: Do not double your dose to make up for the missed one.

Missed Dose Guidelines for Injectable Semaglutide (Ozempic, Wegovy):

  • General Instruction: If you miss a dose, take it as soon as you remember. However, if it's almost time for your next scheduled dose, skip the missed dose.
  • Specific Timeframe for Ozempic: For a missed Ozempic dose, it should be taken within 5 days of the missed schedule. If more than 5 days have passed, skip it.
  • Dietary Considerations: Missing a dose does not allow deviation from your dietary plan. Continue to follow your prescribed treatment and dietary guidelines.

Handling and Storage of Semaglutide

  • Store unused semaglutide pens in the refrigerator between 36°F and 46°F. Do not freeze them.
  • After first use, the pen can be kept at room temperature (up to 86°F) for 56 days. 
  • Safely discard used needles in a sharps container and discard pens after 56 days of first use.
  • Keep semaglutide out of reach of children and pets.

Safety Profile of Once-Weekly Semaglutide

The most common side effects with semaglutide are gastrointestinal, including nausea, vomiting, diarrhea, constipation, and abdominal pain. These are usually mild to moderate and subside over time.

The SUSTAIN trials compared safety outcomes between semaglutide, placebo, and active comparators. Key findings include:

  • Overall rates of adverse events were similar with semaglutide and comparators.
  • Gastrointestinal side effects occurred more often with semaglutide but were transient.
  • Serious adverse events and adverse event-led discontinuation were low and similar across arms.
  • No clinically relevant differences were seen in laboratory parameters, vital signs, or ECG.

While generally well-tolerated, semaglutide may increase the risk of diabetic retinopathy complications, so regular eye exams are recommended.


Dr. V and her staff

Once-weekly injectable semaglutide is an efficacious new treatment option for managing type 2 diabetes, either as monotherapy or as an add-on.

Its convenience, favorable adverse effect profile, and dual impact on glucose and weight make it an attractive choice.

While the oral tablets offer greater ease of use, the injectable form provides slightly better glycemic control. However, both formulations are viable options that give providers more tools to individualize diabetes care.


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