Semaglutide & weight loss

Introduction

An obesity drug remains one of the biggest opportunities for pharmaceutical companies, but it has proved to be one of the most elusive to date. Medications approved for weight loss by the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other regulatory bodies have had a troubled history. Several approved drugs have been withdrawn following serious adverse events. Various amphetamines were withdrawn for addiction, palpitations, and other side-effects. Fenfluramine and dexfenfluramine were withdrawn because of heart valve damage. An increase in major adverse cardiovascular events prompted the withdrawal of sibutramine in Europe and the US. Rimonabant reduced body weight and ameliorated some cardiovascular risk factors, but it was withdrawn because of adverse psychiatric issues. Drugs that have retained approval, such as Orlistat, have severe and debilitating gastrointestinal side-effects, which have limited their use.

I have written about two diet drugs in recent years. In September 2018, I covered a report from the European Society of Cardiology conference (Ref 1). A diet drug was presented at a cardiology conference because it was being claimed to be the first weight-loss drug deemed safe for heart health with long term use. The weight loss difference at one year was 4.2kg in the drug group and 1.4kg in the placebo group. The drug was called Lorcaserin and it was being marketed under the trade name Belviq. In February 2020 it was announced that lorcaserin was being withdrawn from the US market due to increased occurrence of cancer (Ref 2).

In 2015, I reported on a drug called liraglutide (Ref 3). It was approved by the EMA for type 2 diabetes (T2D) in July 2009 and it was approved by the FDA for T2D in January 2010. It was approved by the FDA for obesity on 29th December 2014, where it is marketed as “Saxenda.” It was approved by the EMA on 23rd January 2015 for obesity. The manufacturer is Novo Nordisk.

This week's note is about semaglutide – also made by Novo Nordisk. Liraglutide and semaglutide are both drugs for T2D, which are now being used/researched for obesity (semaglutide is not yet approved). The drugs are injected into the stomach – liraglutide daily and semaglutide weekly. Both drugs belong to a class of drugs called “incretin mimetics” because these drugs mimic the effects of incretins. Incretins are hormones produced and released into the blood by the intestine in response to food. The incretin of key relevance with liraglutide is GLP-1 (Glucagon-Like-Peptide-1). GLP-1 increases the release of insulin from the pancreas, slows absorption of glucose from the gut and reduces the amount of glucose being produced by the liver. All three actions are intended to reduce levels of glucose in the blood stream – hence their use for T2D.

The liraglutide dose for T2D is typically 1.2mg per day. The dose for obesity is 3mg per day. The liraglutide trial was 56 weeks long (with a 12 week follow-up period). Both the drug and placebo group were given the same diet and exercise regime to follow. The drug group lost an average of 8.40kg; the placebo group lost an average of 2.8kg. Those were significant differences.