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 variability1.
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
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