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Cardiovascular outcomes with GLP-1 receptor agonists

28 May 2019This document reviews the evidence from the major cardiovascular clinical trials for GLP-1 receptor agonists.
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Refrigerated Storage

OzempicNovo Nordisk

Novo Nordisk
Ozempic
0.25mg, 0.5mg and 1mg, solution for injection in pre-filled pen

The manufacturer does not hold stability data in addition to that provided in the Summary of Product Characteristics (SPC). Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

21 July 2020
London MI service

New Medicines

RybelsusType 2 diabetes mellitus - once-daily oral treatment

Information

Rybelsus
New formulation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

Launched
Launched
Launched
August 2020
Aug 20Launched in the UK. Price: 3mg, 30=£78.48; 7mg, 30=£78.48; 14mg, 30=£78.48 [37].
Apr 20Launch of Rybelsus® is expected to take place in the first EU countries in H2 2020 [36].
Apr 20Approved in EU [35].
Jan 20Recommended for EU approval by CHMP - the full indication is "for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance or contraindications; in combination with other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1" [34].
Sep 19List price in the US announced at $26 per day, or $772 per 30 tablets across all doses—a price “in-line with injectables” from the same class [31].
Sep 19Approved in the US for adults with T2DM who are not achieving A1C goal with current antidiabetic treatment. The FDA is still reviewing application for an additional indication to reduce the risk of MACE in adults with T2DM and established CVD. [30]
Apr 19Filed in the EU [23]
Mar 19Second NDA filed in US for reduction in risk of MACE in adults with T2DM and established CVD. A decision is anticipated by Q1 2020 [22].
Mar 19Novo has filed semaglutide with the FDA as an oral daily GLP-1. It is using a priority review voucher that will see the FDA review period shortened to six months, so a decision should be expected by Q4 2019 [20].
Feb 19Novo has announced plans to file in the US by the end of Q1 2019, and will use a priority review voucher to accelerate the review process, with the aim of achieving approval by the end of the year [19].
Jun 18Manufacturer hopes to launch in 2020 [14].
Feb 18Will be filed in the EU using the centralised procedure [12].
Feb 18Data from the PIII PIONEER trials are expected throughout 2018 with regulatory submission in 2019 [11].
Mar 16Listed as PIII in company pipeline [7].
Nov 15NCT02607865 (PIONEER 3) not yet open to recruitment. The study is anticipated to start in Feb 16 and complete in Aug 18 [6].

Category

Long-acting GLP-1 analogue
Currently 3.8 million people in the UK are diagnosed with diabetes (90% type 2), and it is estimated that a further 1 million people with type 2 diabetes have not yet been diagnosed [23].
Type 2 diabetes mellitus - once-daily oral treatment
Oral

Trial or other data

Oct 19Semaglutide is a GLP-1 analogue that can help lower blood glucose. It may have a low risk of hypoglycaemia and may induce weight loss by decreasing appetite and food intake. The oral formulation of semaglutide is provided in a tablet formulation with SNAC, an absorption-enhancing excipient included in the Eligen® Carrier Concept [3,4].
Sep 19PIII PIONEER 2 RCT (n=787) found that oral semaglutide (SG) provided superior reductions in HbA1c versus empagliflozin at week 26 (difference -0.4%, p<0.0001). SG also linked to superior weight loss at week 52 (-4.7 vs -3.8 kg, p=0.0114), but significant difference was not achieved at week 26 [33].
Sep 19PIII PIONEER 8 RCT (n=549) found that oral semaglutide 3 mg, 7 mg and 14 mg improved HbA1c vs placebo (difference -0.5%, -0.9% and -1.2% respectively, p<0.001) as well as body weight (-0.9kg, -2.0kg, and -3.3kg, p<0.0001). Nausea occurred in 11.4-23.2% patients with semaglutide [32].
Sep 19In the US, a draft report from the Institute for Clinical and Economic Review (ICER) concluded that oral semaglutide plus background therapy would underperform the SGLT-2 inhibitor, empagliflozin, in cost effectiveness, as measured by quality-adjusted life years gained. ICER evaluation of clinical trial data for oral semaglutide vs empagliflozin, liraglutide, and sitagliptin concluded that oral semaglutide provided incremental benefit in preventing MACE but that MACE prevention is only part of the treatment puzzle, and other treatments may provide better overall benefit and at lower cost. The final report is due Dec 19 [29].
Jun 19Results of PIONEER 6 (n=3,183) are published; the study found semaglutide was non-inferior to placebo for the composite outcome of death from CV disease, non-fatal MI or non-fatal stroke (after median 15.9 months rate = 3.8% for semaglutide vs 4.8% for placebo, HR 0.79, 95% CI 0.57-1.11, p<0.001 for non-inferiority) [28].
Jun 19Results of PIONEER 1 (n=703) are published; the study found that semaglutide reduced HbA1c (3mg, 7mg & 1 mg doses) and improved weight loss (14mg dose) vs placebo (-1.4% and -2.6kg treatment difference for 14 mg vs placebo, p<0.001 for both). The safety profile was consistent with other GLP-1 receptor agonists [27].
Jun 19Results of PIONEER 7 (n=504) are published; at week 52 the odds of achieving an HbA1c < 7% was significantly better with flexible dose adjustments of oral semaglutide (3, 7, or 14 mg per day) than sitagliptin (OR, 4.40, 95% CI 2.89–6.70, p<0.0001) [26].
Jun 19Results of PIONEER 5 (n=324) are published; at 26 weeks, oral semaglutide (14 mg per day) was superior to placebo in decreasing HbA1c from baseline (estimated treatment difference: −0.8 percentage points, 95% CI −1.0 to −0.6; p<0.0001) [25].
Jun 19Results of PIONEER 4 (n=711) are published; at week 26, semaglutide was non-inferior to liraglutide and superior to placebo in decreasing HbA1c, (-1.2%, -1.1% and -0.2%, respectively) and superior in decreasing BMI vs liraglutide and placebo (difference −1.5 and−4.0 kg; p<0.0001) [24].
May 19Novo Nordisk initiate PIII PIONEER 4 (NCT02863419) trial to investigate the efficacy and safety of oral semaglutide vs SC liraglutide and vs placebo. Estimated primary completion date is Apr 18 [8].
Mar 19Results of PIII PIONEER 3 (n=1864) are published; oral semaglutide (7 mg/d and 14 mg/d), vs sitagliptin, resulted in significantly greater reductions in HbA1c over 26 weeks (differences from baseline, -0.3% and -0.5%, respectively; p<0.001 for both). No significant benefit was noted with 3-mg/d dosage [21].
Oct 18PIII trial PIONEER 8 results announced: 52-week trial investigated efficacy and safety of 3, 7 and 14 mg oral semaglutide compared with placebo in 731 people with type 2 diabetes with mean baseline of 8.2%. Those treated with 3, 7 and 14 mg oral semaglutide achieved reductions in HbA1c of 0.6%, 1.0% and 1.4% respectively, compared to no reduction (0.0%) in placebo group [18].
Aug 18Positive data announced from PIII PIONEER 5 trial (NCT02827708) in 324 pts with T2DM and moderate renal impairment who are on a stable dose of metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin. The trial demonstrated superior reductions in HbA1c with semaglutide 14mg od vs. placebo at week 26 (-1.1% vs. -0.1%, ). The number of pts who acheived target HbA1c was 64% with semaglutide vs. 21% with placebo. Pts who took semaglutide lost ~3.7 kg vs. 1.1kg with placebo. Semaglutide was well-tolerated by pts with moderate renal impairment and the most common adverse event for oral semaglutide was mild to moderate nausea.[17]
Jul 18Results of PIII study published in Diabetes Care. RCT (n=705) found once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c (from-1.1 to -1.9%) compared with liraglutide (-0.5 to-1.3%) or placebo (all p<0.001) at 26 weeks, but with higher frequency of GI adverse effects (32.8–54.0% & 21.9–41.5%,respectively) [16].
Jun 18PIII study (PIONEER 3) finds oral semaglutide resulted in larger HbA1c reductions than sitagliptin in T2DM. At 26 and 78 weeks people treated with oral semaglutide experienced statistically significant reductions in HbA1c of 1.1% and 0.7% with 7mg and 1.4% and 1.1% with 14mg vs 0.8% and 0.4% [15].
Jun 18PIONEER 3 trial expected to readout before Q3 2018.[14]
Jun 18Novo Nordisk reported the results of two PIII trials, PIONEER 4 (semaglutide vs. liraglutide injection or placebo) and PIONEER 7 (semaglutide vs. sitagliptin). PIONEER 4 was a yearlong double-blinded trial in 711 pts with T2DM (not controlled by metformin +/- SGLT-2 inhibitor). It met its primary objective, showing a non-inferior reduction in HbA(1c) of 1.2% at wk 52 vs. 0.9% with Victoza. Reduction in body weight with semaglutide was 5kg at 52 weeks vs. 3.1kg with Victoza and 1.2kg for placebo. PIONEER 7 also achieved its primary endpoint. Pts in the semaglutide group experienced reduction in HbA1c of 1.4% vs. 0.7% with Januvia at week 52. In addition, 63% of pts given semaglutide achieved target HbA1c of <7% at 52 weeks vs. 28% of pts given Januvia. Reduction in body weight at week 52 was 2.9kg with semaglutide vs. 0.8kg with Januvia.[14]
May 18Results from PIII PIONEER 2 (NCT02863328) trial reported the primary endpoint was met with oral semaglutide 14mg daily demonstrating a statistically significant and superior improvement in HbA1c (1.4%) vs. empagliflozin 25mg daily (0.9%) at 26 weeks. Difference in weight loss was not statistically significant at 26 weeks - 4.2kg with semaglutide vs 3.8kg with empagliflozin, but was at 52 weeks - 4.7kg vs 3.8kg. Oral semaglutide was well-tolerated with a profile consistent with GLP-1-based therapy. The most common adverse event was mild to moderate nausea, which diminished over time. The proportion of subjects who discontinued treatment due to adverse events was 11% with oral semaglutide vs. 4% with empagliflozin [13].
Feb 18Headline results of PIONEER 1 trial announced. The trial (n=703) achieved its primary endpoint by demonstrating significant and superior improvements in HbA1c in patients with type 2 diabetes for all three doses (3, 7 and 14mg) of oral semaglutide vs placebo. The 14 mg dose of oral semaglutide also demonstrated significant and superior weight loss vs placebo. Oral semaglutide appeared to have a safe and well-tolerated clinical profile. The most common adverse event for all three oral semaglutide doses was mild to moderate nausea, which diminished over time. Premature treatment discontinuation due to adverse events ranged from 2% to 7% with oral semaglutide, vs 2% with placebo [11].
Jan 18Estimated primary completion dates are March 18 for PIONEER 2 (NCT02863328), PIONEER 3 (NCT02607865) and PIONEER 4 (NCT02863419), May 18 for PIONEER 5 (NCT02827708), Oct 18 for PIONEER 6 (NCT02692716), Aug 18 for PIONEER 8 (NCT03021187), and PIONEER 9 (NCT03018028), and July 18 for PIONEER 10 (NCT03015220). PIONEER 1 (NCT02906930) completed Dec 17 [10].
Oct 17Results of PII dose-ranging trial (NCT01923181) published in JAMA. RCT (n=632) reports once-daily oral semaglutide (dose range 2.5 to 40mg od) produced mean change in HbA1c level from baseline to week 26 of −0.7 to −1.9%, -1.9% with sc semaglutide and -0.3% with placebo [9].
Sep 16Novo Nordisk initiate PIII PIONEER 7 (NCT02849080) trial to investigate the efficacy and safety of oral semaglutide using a flexible dose adjustment based on clinical evaluation, compared with sitagliptin, in patients with type 2 diabetes. Estimated primary completion date is Mar 19 [8].
Sep 16Novo Nordisk initiate PIII PIONEER 5 (NCT02827708) trial to investigate the efficacy and safety of oral once-daily dosing of semaglutide 14mg tablet vs placebo, in patients with T2DM and moderate renal impairment who are on a stable dose of metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin. Estimated primary completion date is Jan 18 [8].
Aug 16Novo Nordisk initiate PIII PIONEER 1 (NCT02906930) trial to investigate the efficacy and safety of three dose levels of once-daily oral dosing of semaglutide, in patients with T2DM treated with diet and exercise only. Estimated primary completion date is Nov 17 [8].
Jul 16Novo Nordisk initiate PIII PIONEER 2 (NCT02863328) trial to investigate the efficacy and safety of oral once-daily dosing of semaglutide 14mg tablet vs empagliflozin 25mg tablet, both in combination with metformin, on glycaemic control in patients with T2DM. Estimated primary completion date is Mar 18 [8].
Feb 16Novo Nordisk initiate PIII PIONEER 3 (NCT02607865) trial to investigate the long-term safety of oral semaglutide versus sitagliptin in patients with T2DM. Estimated primary completion date is Mar 18 [8].
Jan 16Novo Nordisk plans to initiate PIII PIONEER 8 trial (NCT03021187) to investigate the efficacy and safety of oral semaglutide vs placebo in patients with T2DM treated with insulin. Estimated primary completion date is Jan 18 [8].
Jan 16Novo Nordisk plans to initiate PIII PIONEER 6 trial (NCT02692716) to investigate the CV safety of oral semaglutide in patients with T2DM. Estimated primary completion date is Apr 18 [8].
Nov 15Novo Nordisk plans a PIII trial in type 2 diabetes in countries including US and UK (NCT02607865) [5].
Aug 15Novo Nordisk announced plans to initiate a global PIII3a development program (PIONEER) with oral semaglutide for type 2 diabetes. The PIONEER program will include 6 safety and efficacy trials and one trial for evaluating the cardio-vascular safety of oral semaglutide in approximately 8,000 pts with type 2 diabetes. The first trial in the programme is planned for initiation in Q1 2016 and will investigate the efficacy and safety of once-daily oral semaglutide doses of 3 mg, 7 mg and 14 mg vs. once-daily oral anti-diabetic sitagliptin dose of 100 mg. The remaining six trials of the PIONEER programme are all expected to be initiated during 2016. Completion dates for the trials are not yet available [3,4].
Feb 15Positive data from PII dose-ranging trial (NCT01923181) of OG217SC administered in 600 people with type 2 diabetes over the course of 26 weeks. All doses of oral semaglutide were statistically significantly superior to the placebo. [1]

Evidence based evaluations

Wegovy (US)Obesity in patients without diabetes mellitus - SC formulation

Information

Wegovy (US)
New formulation and new indication
Novo Nordisk
Novo Nordisk

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Jun 21Launched in the US. Price not released but the company said it plans to introduce Wegovy at a similar list price to liraglutide (Saxenda). That drug costs between $1,300 and $1,600 per month [18].
Jun 21Trade name for semaglutide 2.4mg in US is Wegovy [17].
Jun 21FDA approves once-weekly semaglutide 2.4 mg self-injection for chronic weight management [16]
Dec 20Filed in EU [12]
Dec 20Novo Nordisk files NDA with the US FDA for subcutaneous semaglutide 2.4 mg, for chronic weight management [11]
Nov 19Analysts predict approval of semaglutide for obesity in 2022 [6].
Jun 17Novo Nordisk expects the PIII programme to begin in 2018 [3].

Category

Once-weekly human GLP-1 (glucagon-like peptide-1) analogue - 2.4mg dose
From 2012 figures, 24% of men and 25% of women are obese. This had increased from 13% and 16% respectively since 1993. A further 42% of men and 32% of women were overweight. This means most adults in England are overweight or obese. The UK currently has the highest prevalence in Europe [1].
Obesity in patients without diabetes mellitus - SC formulation
Subcutaneous injection

Further information

Yes
March 2022

Trial or other data

Mar 21Results of PIII STEP 4 trial (NCT03548987) reported in JAMA [15].
Feb 21Results of PIII STEP 3 study published in JAMA [14].
Jun 20PIII STEP 3 trial met both of its primary endpoints. A statistically significantly greater weight loss was achieved with semaglutide 2.4 mg as an adjunct to intensive behavioural therapy (IBT) from a mean baseline bodyweight of 105.8 kg, of 16.0% vs 5.7% with placebo plus IBT after 68 weeks. More of those treated with semaglutide 2.4 mg achieved a weight loss of 5% or more after 68 weeks as an adjunct to IBT compared with placebo plus IBT (86.6% vs 47.6%) [9].
Jun 20In PIII Step 2 trial, both primary endpoints were reached with a statistically significant greater weight loss of 9.6% at 68 weeks with semaglutide 2.4mg from a mean baseline bodyweight of 99.8 kg (7% vs 3.4% weight loss with placebo). Of those who received semaglutide 2.4 mg, 68.8% achieved a weight loss of 5% or more after 68 weeks, compared to 28.5% with placebo [9].
Jun 20results from PIII STEP I trial found that it met both primary endpoints. A statistically significant and superior reduction in body weight was achieved with sc semaglutide 2.4 mg compared to placebo after 68 weeks. People treated with semaglutide achieved a weight loss of 14.9%, from a mean baseline body weight of 105.3 kg, compared to a 2.4% weight loss with placebo. In addition, 86.4% of those who received sc semaglutide 2.4 mg reached a weight loss of 5% or more after 68 weeks, compared to 31.5% with placebo [8].
May 20Results of PIII STEP 4 trial (NCT03548987) report primary objective was achieved with all people (n=902) randomised to continued treatment with SC semaglutide 2.4mg for 48 weeks (after the run-in period) achieved additional mean weight loss of 7.9% vs placebo where people regained 6.9% of the body weight. When evaluating the effects of treament, people who continued treatment with SC semaglutide 2.4 mg achieved an additional mean weight loss of 8.8% whereas people on placebo regained 6.5%. The treatment difference was statistically significant. People who stayed on SC semaglutide 2.4 mg for 68 weeks achieved a weight loss of 18.2%. In the trial, semaglutide appeared to have a safe and well-tolerated profile. The most common adverse events among people treated with semaglutide were GI events. Most events were transient and mild or moderate in severity [10].
Nov 19PIII SELECT trial is recruiting & expects to complete collection of primary outcome data in Sep 23 [7].
Sep 19PIII STEP 8 trial to compare the efficacy of semaglutide once a week on body weight in people taking or people taking liraglutide once every day starts (NCT04074161). 336 patients will be recruited in the US [6].
Jan 19PIII STEP trial to investigate the effect and safety of semaglutide (SC) once-weekly in East Asian volunteers with obesity starts (NCT03811574). Change in participant´s body weight and approximately 5% body weight reduction from baseline are the defined primary endpoints of the study. The randomised, quadrapule masked trial intends to enrol 400 patients in Japan and South Korea [6].
Oct 18PIII SELECT trial to evaluate if semaglutide reduces the risk of having cardiovascular events, in patients with overweight or obesity and with prior cardiovascular disease starts (NCT03574597). Evaluation of the time to first occurrence of a composite endpoint consisting of: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke is the defined primary endpoint of the trial. The open label trial is enrolling approximately 17,500 patients [6].
Aug 18PIII STEP 3 trial to study the effect and safety of semaglutide 2.4 mg once-weekly as adjunct to intensive behavioural therapy in patients with obesity starts (NCT03611582). The study intends to enrol 600 patients in the US, & collection of primary outcome data should complete Mar 20 [4].
Jul 18PIII STEP 5 trial to study two-year effect and safety of semaglutide 2.4 mg once-weekly in patients with obesity starts (NN9536-4378; EudraCT2017-003726-32). The study intends to enrol 300 patients in the US, EU and Canada [5].
Jun 18PIII STEP 2 trial to evaluate the effect of semaglutide subcutaneous (s.c.) 2.4 mg once-weekly, in patients with overweight or obesity and type 2 diabetes starts (NCT03552757). Evaluation of the change in body weight and number of subjects who achieve body weight reduction greater than or equal to 5% are the defined primary endpoints of the trial. The trial intends to enrol approximately 1200 patients in the US, Canada, Greece, Japan, Russia, Spain, and the UK [4].
Jun 18PIII STEP 4 trial to compare the effect of semaglutide 2.4mg once-weekly versus semaglutide placebo as an adjunct to reduced-calorie diet and increased physical activity in subjects with overweight or obesity who have reached target dose of semaglutide during the run-in period, on body weight starts (NCT03548987). The trial is enrolling 1,200 patients in countries including the US & EU [4].
Jun 18PIII STEP 1 trial to compare the effect of semaglutide s.c. 2.4 mg once-weekly versus semaglutide placebo as an adjunct to a reduced-calorie diet and increased physical activity in subjects with overweight or obesity on body weight starts (NCT03548935). The trial is enrolling approximately 1950 patients in countries including the US & EU (plus UK) [4].
Jun 17Novo Nordisk reports up to 13.8% weight loss in people with obesity receiving semaglutide in PII trial (NCT02453711). In the trial, 957 people with obesity were randomised to treatment with doses of semaglutide between 0.05 to 0.4 mg/day or placebo. Liraglutide 3.0 mg/day was included for comparison. Approximately 100 people were included in each active treatment arm in combination with diet and exercise. All people in the trial were treated for 52 weeks followed by a 7-week follow-up period. From a mean baseline weight of around 111 kg and a body mass index of approximately 39 kg/m2, a weight loss up to 17.8 kg was observed after 52 weeks of treatment with semaglutide. This corresponded to an estimated 13.8% weight loss compared to the weight loss of 2.3% achieved by diet, exercise and placebo alone, with all treatment arms adjusted for people discontinuing treatment in the study. The results from the liraglutide 3.0 mg treatment arm were broadly in line with previously reported data [3].
Mar 17PII study (NCT02453711) completes [2].
Oct 15PII trial assessing safety and efficacy of once-daily subcutaneous semaglutide in obese patients without diabetes mellitus starts (NCT02453711). Relative change in body weight at 52 weeks is the primary endpoint. 957 patients will be enrolled in the US, Australia, Belgium, Canada, Germany, Israel, Russia and the UK [2].

Evidence based evaluations

Type 2 diabetes mellitus - high-dose 2mg SC formulation

Information

New formulation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
May 21NovoNordisk announces resubmission of its application to the FDA for licence extension for a 2mg once-weekly dose [6]
Mar 21Novo Nordisk receives a refusal to file letter from the US FDA. Novo expect to resubmit the application in Q2 2021 [5].
Jan 21Novo Nordisk has filed for label extension for Ozempic 2mg in the US [4].
Dec 20Novo Nordisk have submitted a label extension application to the European Medicines Agency (EMA) for the existing marketing authorisation for 2mg dose of semaglutide once weekly for Type 2 diabetes [3].

Category

Glucagon-like peptide-1 (GLP-1) analogue - 2mg once weekly dose in a penfill device. Ozempic is currently available as a 0.25mg, 0.5mg and 1mg prefilled pen.
There are 3.8 million people who have been diagnosed with diabetes in the UK; 90% have T2DM [1].
Type 2 diabetes mellitus - high-dose 2mg SC formulation
Subcutaneous injection

Trial or other data

Jul 21Results of PIII SUSTAIN FORTE RCT reported in The Lancet [5].
Jun 21Results of the PIII SUSTAIN FORTE trial (n=961) presented at the American Diabetes Association 2021 virtual scientific sessions. Patients taking the higher dose (2mg) semaglutide achieved HbA1c reduction of 2.2% vs 1.9% in the 1mg dose arm. Weight loss also favoured the higher dose with patients on the 2mg dose losing 6.9kg vs 6kg with the 1mg dose (statistically significant). Side effect rates were similar across both doses. Results will be published in The Lancet Diabetes & Endocrinology [7]
Jan 20PIII SUSTAIN FORTE study is recruiting. Collection of primary outcome data (change in HbA1c) is due to complete Sep 20 [2].
Jun 19PIII SUSTAIN FORTE study (NCT03989232) starts. It will compare the effect of two doses of semaglutide (1.0 mg and 2.0 mg) in people with type 2 diabetes (T2D). People taking part in the study will take the medicine together with their current diabetes medicine (sulphonylurea and/or metformin). The study will last for about 49 weeks. 964 adults will be recruited in the US, Bulgaria, Canada, Czechia, Hungary, Greece, Japan, Poland, Puerto Rico, Slovakia and Ukraine [2].

Obesity in children aged 12 to 17 years - SC formulation

Information

Licence extension / variation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Once-weekly human GLP-1 (glucagon-like peptide-1) analogue - 2.4mg dose
In 2016, the Health Survey for England found that 23% of children aged 11 to 15 were obese, with a higher rate of obesity observed in boys (26%) compared to girls (20%) [1].
Obesity in children aged 12 to 17 years - SC formulation
Subcutaneous injection

Rybelsus Type 2 diabetes mellitus - 25mg and 50mg formulations

Information

Rybelsus
New formulation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Long-acting GLP-1 analogue
Currently 3.8 million people in the UK are diagnosed with diabetes (90% type 2), and it is estimated that a further 1 million people with type 2 diabetes have not yet been diagnosed [1].
Type 2 diabetes mellitus - 25mg and 50mg formulations
Oral

Alzheimer's disease

Information

Licence extension / variation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None

Category

Long-acting GLP-1 analogue
The age-standardised population prevalence of dementia in people 65 years of age and older in the UK is 7.1%, of which 50% are Alzheimers disease [2].
Alzheimer's disease
Oral

Ozempic Peripheral arterial disease (PAD) in patients with diabetes

Information

Ozempic
Licence extension / variation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

GLP1-receptor analogue administered by subcutaneous injection
Peripheral arterial disease (PAD) affects 4-12% of people aged 55-70 years and 15-20% of people aged over 70 years. Diabetes is one of several risk factors [1].
Peripheral arterial disease (PAD) in patients with diabetes
Subcutaneous injection

Ozempic Non-alcoholic steatohepatitis (NASH) with stage 2 or 3 liver fibrosis

Information

Ozempic
Licence extension / variation
Novo Nordisk
Novo Nordisk

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Once-weekly human GLP-1 (glucagon-like peptide-1) analogue
Fatty liver disease is divided into alcohol-related fatty liver disease, and non-alcoholic fatty liver disease (NAFLD). The only difference between the two is the alcohol. A threshold of <20 g of alcohol per day in women and <30 g in men is usually used to allow a diagnosis of NAFLD. When inflammation is present, this becomes non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. In Europe prevalence of NAFLD is 20-30% and NASH is 5% [1].
Non-alcoholic steatohepatitis (NASH) with stage 2 or 3 liver fibrosis
Subcutaneous injection