The New England Journal of Medicine has recently published the results of a long term study investigating the safety and efficacy of tirzepatide in reducing weight and delaying progression to type 2 diabetes.
The study recruited 2,539 participants with obesity, of whom 1,032 also had prediabetes. The study had four arms, tirzepatide at 5 mg, 10 mg, or 15 mg and placebo. Follow up was planned for 3 years. The last on-treatment review was performed at 176 weeks with an additional follow up after 17 weeks off treatment. At 176 weeks, the three treatment arms produced statistically significant weight loss of between 15.4% and 22.9% depending on the dose. (Table S4) And fewer participants in the treatment group received a diagnosis of type 2 diabetes.
The study concluded that tirzepatide treatment demonstrated a "substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes".
After the 17 week off-treatment phase, overall weight loss was reported to be between 12.3% and 17.9% (Table S5). Approximately 20% of the weight lost during the treatment phase had been regained. The confidence intervals (Fig 1B) for the data points at week 193 are discrete for each tirzepatide strength from the 176 week data point, indicating that the weight gain off treatment is statistically significant.
Weight gain after stopping weight loss treatments has been demonstrated for previous treatments including orlistat, sibutramine (withdrawn in 2010 over cardiovascular safety concerns), rimonabant (withdrawn in 2008 due to concerns over psychiatric side effects) and semaglutide.
Action: Clinicians will be aware that sustained weight loss requires long term lifestyle modification, including a calorie controlled diet and increased physical activity. The results of this study are not surprising; the weight gain observed during the off-treatment phase highlights how crucial it is for lifestyle changes to be maintained.
The Faculty of Sexual and Reproductive Health (FSRH) has published a clinical statement advising that individuals use contraception whilst using GLP-1 agonists. There is also additional advice for individuals using tirzepatide.
The statement notes that there is a lack of safety evidence for this group of drugs in pregnancy and as such contraception should be used during treatment with all GLP-1 agonists. Details of the 'washout' period should also be shared if pregnancy is planned, the time period before ending treatment and when the medication is cleared fully from the body.
Within this class of medicines, tirzepatide is the only drug that has been found to have a clinically significant effect on the bioavailability of oral contraceptives. It is advised that consideration be given to switching to a non-oral methods of contraception, or adding a barrier method of contraception for four weeks after initiation and for four weeks after each dose increase.
Finally within this statement, it is recommended that individuals who experience severe diarrhoea or vomiting during use of GLP-1 agonists should follow existing recommendations with respect to maintaining effect contraception.
Action: Clinicians who commence or review patients using GLP-1 agonists should be aware of these recommendations and ensure that patients are suitably advised and offered appropriate contraception where necessary.
Thanks to Rita Shah for spotting this article.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on newly licensed medicines.
Netarsudil / latanoprost (Roclanda®) has been accepted for restricted use in the treatment of elevated intraocular pressure (IOP) in adult patients with primary open-angle glaucoma or ocular hypertension for whom monotherapy with a prostaglandin or netarsudil provides insufficient IOP reduction. The restriction limits use to patients for whom treatment with a prostaglandin analogue alone provides insufficient IOP reduction, only if:
- the patient has then tried a fixed-dose combination treatment and it has not sufficiently reduced IOP, or
- a fixed-dose combination treatment containing beta-blockers is unsuitable
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on newly licensed medicines.
Ciclosporin (Cequa®) drops have been accepted for restricted use in the treatment of moderate-to-severe Dry Eye Disease (keratoconjunctivitis sicca) in adult patients who have not responded adequately to artificial tears. The restriction limits use to cases of severe keratitis in adult patients.
Relugolix, estradiol, norethisterone tablets (Ryeqo®) has been accepted for use in adult women of reproductive age for symptomatic treatment of endometriosis in women with a history of previous medical or surgical treatment for their endometriosis.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on newly licensed medicines.
Vibegron (Obgemsa®) has been accepted for use in the symptomatic treatment of adult patients with overactive bladder (OAB) syndrome. It is noted that this treatment offers an additional choice in the therapeutic class of beta-3 adrenergic receptor agonists.
Levodopa / carbidopa / entacapone intestinal gel (Lecigon®) has been rejected for the treatment of advanced Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when available oral combinations of Parkinson medicinal products have not given satisfactory results. The submitting company did not present a sufficiently robust clinical or economic analysis to gain acceptance by SMC.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
