GLP‑1 news from 2019
12 dated, sourced GLP-1 developments from 2019: approvals, trial results, prices, lawsuits, compounding and culture.
- Regulation
Rybelsus becomes the first GLP-1 pill approved in the US for type 2 diabetes
The FDA approved Rybelsus (semaglutide) tablets on September 20, 2019, for adults with type 2 diabetes, the first GLP-1 receptor agonist sold as a pill instead of an injection. Approved strengths were 3 mg, 7 mg and 14 mg, taken once daily on an empty stomach with up to 4 ounces of plain water and followed by a 30-minute wait before food, drinks or other oral medicines. Side effects reported in at least 5% of patients included nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation.
- Science
Rybelsus arrived in 2019 with strict fasting rules that a 2026 rival pill avoided
The FDA approved Rybelsus (semaglutide) on September 20, 2019, as the first oral GLP-1 for type 2 diabetes, with label instructions to take it on an empty stomach with no more than 4 ounces of plain water and then wait 30 minutes before eating, drinking or taking other medicines. Orforglipron (Foundayo), approved April 1, 2026, became the first oral GLP-1 for weight loss with no food or water restrictions. In its 72-week trial, the 36 mg orforglipron dose produced average weight loss of 12.4%.
- Business
Oral semaglutide matches injected liraglutide for A1C and beats it on weight in 711-patient trial
The Lancet published PIONEER 4, a 711-patient phase 3a trial comparing oral semaglutide 14 mg with subcutaneous liraglutide 1.8 mg and placebo in adults with type 2 diabetes. At week 26, A1C fell by 1.2 percentage points with oral semaglutide, 1.1 with liraglutide and 0.2 with placebo, meeting the trial's non-inferiority bar, while weight fell by 4.4 kg, 3.1 kg and 0.5 kg. The trial was funded by Novo Nordisk, and a correction notice was published in the same journal issue.
- Research and trials
First human trial of Akkermansia muciniphila reports safety and mixed metabolic results
Nature Medicine published the first human trial of Akkermansia muciniphila, a gut bacterium given as an oral supplement, on July 1, 2019. In a randomized, double-blind, placebo-controlled pilot that 32 people completed, three months of pasteurized A. muciniphila was safe and well tolerated and improved insulin sensitivity by 28.62%, lowered insulinemia by 34.08% and reduced total cholesterol by 8.68%. The 2.27 kg difference in body weight versus placebo did not reach statistical significance (P = 0.091).
- Research and trials
PIONEER 6 finds oral semaglutide does not add heart risk in type 2 diabetes
Major cardiovascular events occurred in 61 of 1,591 patients taking oral semaglutide (3.8%) and 76 of 1,592 taking placebo (4.8%), a hazard ratio of 0.79 with a 95% confidence interval of 0.57 to 1.11. The 3,183-patient trial was built to rule out an 80% higher risk, not to prove a benefit. Novo Nordisk funded the study, published June 11, 2019.
- Regulation
Trulicity gains cardiovascular indication after REWIND trial cuts events in type 2 diabetes
The REWIND trial found that dulaglutide 1.5 mg reduced major adverse cardiovascular events in adults with type 2 diabetes, from 13.4 percent to 12.0 percent, a hazard ratio of 0.88, over a median 5.4 years. Most of the benefit came from a 24 percent reduction in nonfatal stroke. The results supported a new cardiovascular indication for Trulicity.
- Research and trials
Liraglutide (Victoza) lowered A1C in children and teens with type 2 diabetes, trial finds
A 134-patient trial published April 28, 2019, in the New England Journal of Medicine found that liraglutide (Victoza), added to metformin, lowered A1C by 1.06 percentage points more than placebo at 26 weeks in patients aged 10 to under 17 with type 2 diabetes. The gap widened to 1.30 percentage points at 52 weeks, and gastrointestinal side effects were more common with liraglutide.
- Research and trials
Oral semaglutide 7 mg and 14 mg beat sitagliptin on blood sugar and weight in PIONEER 3 trial
In the PIONEER 3 trial published in JAMA on April 16, 2019, adults with type 2 diabetes taking oral semaglutide 7 mg or 14 mg once daily had greater reductions in HbA1c and body weight at 26 weeks than those taking sitagliptin 100 mg. The 7 mg dose lowered HbA1c by an extra 0.3 percentage points and the 14 mg dose by an extra 0.5 points versus sitagliptin, with weight differences of 1.6 kg and 2.5 kg. The 3 mg starting dose did not demonstrate non-inferiority to sitagliptin.
- Regulation
FDA clears Plenity, a hydrogel weight-management device, for adults with BMI 25 to 40
In April 2019 the FDA cleared Plenity, an oral hydrogel made by Gelesis, as a medical device rather than a drug for weight management in adults with a body mass index of 25 to 40 who also diet and exercise. In the 24-week GLOW trial of 436 adults, mean weight loss was 6.4% with Plenity versus 4.4% with placebo, and 59% of the treatment group lost at least 5% of body weight versus 42% on placebo.
- Regulation
Novo Nordisk files oral semaglutide with FDA for type 2 diabetes
On March 26, 2019, Novo Nordisk filed with the FDA for an oral tablet form of semaglutide to control blood sugar and reduce cardiovascular risk in adults with type 2 diabetes. The FDA approved the drug on September 20, 2019 as Rybelsus, the first oral GLP-1 analog for adults with type 2 diabetes, in 3 mg, 7 mg and 14 mg tablets. The cardiovascular risk reduction use was not approved until October 17, 2025.
- Business
Lilly agreed to buy Loxo Oncology for $8 billion in cancer push
Eli Lilly agreed to acquire Loxo Oncology for $8.0 billion in a deal announced January 7, 2019. It is the largest single acquisition in a Lilly deal history that runs from 1985 to 2025, a span of 19 deals with about $30.8 billion in total disclosed value. Loxo added targeted cancer therapies for genetically defined patient groups.
- Business
Novo Nordisk reports 2019 sales of DKK 122 billion and a 47.5% share of the global GLP-1 market
Novo Nordisk's 2019 annual report shows sales of DKK 122.0 billion, up 9% in Danish kroner, and operating profit of DKK 52.5 billion. The company reported a 47.5% value share of the global GLP-1 market in a year that also included approval of oral semaglutide, sold as Rybelsus.