Introducing Ozempic

Article by Donna Itzstein, Pharmacist CDE

Ozempic follows the introduction of other injectable incretin therapies available in Australia.  The Federal drug administration (FDA) in America approved Semaglutide for use in late 2017.  Novo Nordisk was successful in registering Semaglutide (Ozempic) with the Therapeutic Goods Administration (TGA) in August 2019 and with the Pharmaceutical benefits scheme (PBS) in July this year. Semaglutide is indicated for the treatment of type2 diabetes in non-pregnant adults.

The benefits of glucagon like peptide (GLP-1) agonists in the management of type 2 diabetes include weight loss, improved cardiovascular risk and significant improvement in HbA1c. Their appeal is dampened by patient aversion of injections and gastrointestinal effects which take persistence to overcome.

Figure 1 from SUSTAIN trial 1, describes the efficacy of Semaglutide after 30 weeks. As with other GLP-1 agonists there is a significant reduction in HbA1c, fasting blood glucose levels and body weight. Blood glucose levels over a 24-hour period as seen in figure 2 demonstrate lower spikes in blood glucose following meals bringing levels into target and reducing variability^1.

Trulicity (Dulaglutide) is the closest comparator.  Figure 3 from the trial SUSTAIN 7, compares Semaglutide both strengths to Dulaglutide 0.75mg and 1.5mg (0.75mg is not available in Australia). Three key indicators, HbA1c, fasting blood glucose and weight reduction were improved with Semaglutide compared to Dulaglutide.¹ The most frequent adverse reaction reported in GLP-1 agonists is nausea followed by diarrhoea. The rates of nausea in Semaglutide and Dulaglutide are similar around 20% with both reducing with persistence.²

Other observations that may be noted for Semaglutide are an improvement in beta cell function, small increases in heart rate, small reductions in blood pressure and an improvement in lipid profile. These observations are a class effect of GLP-1 agonists.

Worsening of diabetic retinopathy (DR) may occur with rapid improvements in glycaemia.  Worsening DR was found to be significantly more likely in persons with type 2 diabetes treated with semaglutide versus placebo (3.0% versus 1.8%) in the SUSTAIN trial 6. This is a significant finding which resulted in Novo Nordisk adding a caution with use in patients being treated with insulin and with pre-existing DR or increased risk of DR. The incidence of DR for people living with type 2 diabetes is one out of three.³ Incidence increases with the duration of diabetes corresponding to the progression of type 2 diabetes leading to insulin administration.

What happened in this trial? The exclusion criteria differed from the SUSTAIN 1-5 trials. SUSTAIN 6 was a cardiovascular trial and did not exclude existing or risk of DR.  When the data was analysed, patients without pre-existing DR or risk had the same incidence of worsening DR as placebo. Also, patients who had retinopathy complications had a rapid and steep decrease of approximately 2.5% in HbA1c level.⁴

Prescribing details:

• Dosing: Ozempic starting dose is 0.25 mg once weekly for 4 weeks. Then increase to 0.5 mg once weekly.
  • After at least 4 weeks with a dose of 0.5 mg once weekly, increase to 1 mg once weekly to further improve glycaemia if required.
• Storage is in the refrigerator (2°C to 8°C). After first use it may be stored at room temperature 30°C or in a refrigerator (2°C to 8°C).  Once opened, product expiry is 6 weeks. Protect from heat and light.
• Ozempic 0.25 mg, 0.5 mg/dose solution for injection in pre-filled pen is intended dose escalation and maintenance treatment at the 0.5 mg dose. The pen contains 1.5 mL solution. Ozempic 1 mg/dose for injection in pre-filled pen is only able to deliver doses of 1 mg for maintenance treatment. The pen contains 3 mL solution. The kits include sufficient disposable needles. Needles should be changed with each use. Patients will require sharps disposal. Note: This differs from Trulicity which is one dose per pen with a retractable needle.
• There is no dosage adjustment required for elderly <75 years, gender, race or ethnicity, hepatic or renal impairment. It is not recommended in end stage renal failure. Ensure adequate fluid intake during treatment as dehydration may affect renal function. The high incidence of nausea and diarrhoea during the early adjustment time may reduce hydration.
• Ozempic is subsidised on the pharmaceutical benefits scheme one 1.5 or 3ml pen with 5 repeats allowed. Streamline authority is required.

Other tips

• Ozempic is a subcutaneous injection. It is used in the same sites as insulin – stomach, thigh, upper arms. It is not to be given intramuscularly, intravenously or orally. It does not require a longer or thicker needle than insulin with novofine up to 8mm fitting the pens. Appearance: Almost colourless, clear liquid that does not require premixing.
• Novo Nordisk has a dedicated website OzempiCare HCP for patient support and resources and health professional learning. ⁵
• Dosing is once weekly on the same day each week without regard to meals. Your patient can change the day of the week administered as long as the injections are at least 3 days apart. If your patient misses a dose they can take the dose within 5 days, otherwise skip the dose and resume with a single dose on the regular day.
• Hypoglycaemia may occur with use of insulin or sulfonylureas with Ozempic. Risk is lowered by reducing the dose of insulin or sulfonylurea when starting Ozempic.
• Due to the increased incidence, patients with a history of diabetic retinopathy should be monitored for worsening DR and treated according to clinical guidelines.
• Even though Semaglutide like other GLP-1 agonists reduces gastric emptying it does not influence the absorption of other medications. Those examined were warfarin, metformin, digoxin, atorvastatin and oral contraceptives.

Ozempic is a welcome new option into growing collection of treatment options available for your patients living with type 2 diabetes. GLP-1 agonists such as Ozempic are unlikely to become first line therapy for people living with type 2 diabetes due to the cost, they may become an option that is used earlier in the progression of type 2 diabetes. The benefits of weight loss and cardiovascular safety make GLP-1 agonists attractive.

The Australian Product information from Novo Nordisk can be found here

References

1. Novo Nordisk. Ozempic prescribing information. Therapeutic Goods Administration – Prescribing information. [Online] August 28, 2019.
2. Eli Lilly. Trulicity prescribing information. Therapeutic Goods administration: Prescribing information. [Online] July 2019.
3. Diabetic eye disease: A UK Incidence and Prevalence Study. R Mathur, et al. s.l. : RNIB, 2017.
4. SUSTAIN-6: Retinopathy complications may be increased with semaglutide. Rollet, J. San Diego, USA : Endocrine Today, August 2017, American Diabetes Association Scientific Sessions.
5. Novo Nordisk. Ozempic Hub. [Online] [Cited: August 12, 2020.] https://www.ozempic.com.au/.