Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial
Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination. In this randomised,...
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| Veröffentlicht in: | The Lancet (British edition) 2021-05, Vol.397 (10286), p.1736-1748 |
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| creator | Enebo, Lone B Berthelsen, Kasper K Kankam, Martin Lund, Michael T Rubino, Domenica M Satylganova, Altynai Lau, David C W |
| description | Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.
In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18–55 years with a body-mass index 27·0−39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0–168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete.
Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events report |
| doi_str_mv | 10.1016/S0140-6736(21)00845-X |
| format | Article |
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In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18–55 years with a body-mass index 27·0−39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0–168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete.
Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16–4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0–168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16–4·5 mg. AUC0–168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16−4·5 mg had a half-life of 159–195 h, with a median tmax of 24–72 h. Semaglutide 2·4 mg had a half-life of 145–165 h, with a median tmax of 12–24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1–5; estimated treatment difference of −6·0% [95% CI −9·9 to −2·0] for cagrilintide 1·2 mg and −7·4% [−11·2 to −3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference −7·4% [−12·8 to −2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups.
Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination.
Novo Nordisk A/S.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(21)00845-X</identifier><identifier>PMID: 33894838</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Adverse events ; Amylin ; Anti-Obesity Agents - administration & dosage ; Anti-Obesity Agents - pharmacokinetics ; Anti-Obesity Agents - pharmacology ; Antidiabetics ; Arthritis ; Asthma ; Cardiovascular disease ; Clinical trials ; Diabetes ; Dosage ; Double-Blind Method ; Drug dosages ; Drug therapy ; Drug Therapy, Combination ; Exposure ; Female ; Gastrointestinal diseases ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptides - administration & dosage ; Glucagon-Like Peptides - pharmacokinetics ; Glucagon-Like Peptides - pharmacology ; Half-life ; Hormones ; Humans ; Injections ; Investigations ; Islet Amyloid Polypeptide - administration & dosage ; Islet Amyloid Polypeptide - adverse effects ; Islet Amyloid Polypeptide - pharmacokinetics ; Male ; Middle Aged ; Obesity ; Obesity - drug therapy ; Osteoarthritis ; Overweight ; Parameters ; Peptides ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology ; Placebos ; Safety ; Weight ; Weight control ; Weight Loss - drug effects</subject><ispartof>The Lancet (British edition), 2021-05, Vol.397 (10286), p.1736-1748</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>2021. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c308t-268925fe5d318275335eb75899692ce3acc1295476e89ea88b4b5774154570493</citedby><cites>FETCH-LOGICAL-c308t-268925fe5d318275335eb75899692ce3acc1295476e89ea88b4b5774154570493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2522593634?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000,64390,64394,72474</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33894838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Enebo, Lone B</creatorcontrib><creatorcontrib>Berthelsen, Kasper K</creatorcontrib><creatorcontrib>Kankam, Martin</creatorcontrib><creatorcontrib>Lund, Michael T</creatorcontrib><creatorcontrib>Rubino, Domenica M</creatorcontrib><creatorcontrib>Satylganova, Altynai</creatorcontrib><creatorcontrib>Lau, David C W</creatorcontrib><title>Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.
In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18–55 years with a body-mass index 27·0−39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0–168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete.
Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16–4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0–168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16–4·5 mg. AUC0–168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16−4·5 mg had a half-life of 159–195 h, with a median tmax of 24–72 h. Semaglutide 2·4 mg had a half-life of 145–165 h, with a median tmax of 12–24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1–5; estimated treatment difference of −6·0% [95% CI −9·9 to −2·0] for cagrilintide 1·2 mg and −7·4% [−11·2 to −3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference −7·4% [−12·8 to −2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups.
Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination.
Novo Nordisk A/S.</description><subject>Adult</subject><subject>Adverse events</subject><subject>Amylin</subject><subject>Anti-Obesity Agents - administration & dosage</subject><subject>Anti-Obesity Agents - pharmacokinetics</subject><subject>Anti-Obesity Agents - pharmacology</subject><subject>Antidiabetics</subject><subject>Arthritis</subject><subject>Asthma</subject><subject>Cardiovascular disease</subject><subject>Clinical trials</subject><subject>Diabetes</subject><subject>Dosage</subject><subject>Double-Blind Method</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Exposure</subject><subject>Female</subject><subject>Gastrointestinal diseases</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptides - administration & dosage</subject><subject>Glucagon-Like Peptides - pharmacokinetics</subject><subject>Glucagon-Like Peptides - pharmacology</subject><subject>Half-life</subject><subject>Hormones</subject><subject>Humans</subject><subject>Injections</subject><subject>Investigations</subject><subject>Islet Amyloid Polypeptide - administration & dosage</subject><subject>Islet Amyloid Polypeptide - adverse effects</subject><subject>Islet Amyloid Polypeptide - pharmacokinetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Obesity</subject><subject>Obesity - drug therapy</subject><subject>Osteoarthritis</subject><subject>Overweight</subject><subject>Parameters</subject><subject>Peptides</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Placebos</subject><subject>Safety</subject><subject>Weight</subject><subject>Weight control</subject><subject>Weight Loss - drug 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tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial</title><author>Enebo, Lone B ; Berthelsen, Kasper K ; Kankam, Martin ; Lund, Michael T ; Rubino, Domenica M ; Satylganova, Altynai ; Lau, David C W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c308t-268925fe5d318275335eb75899692ce3acc1295476e89ea88b4b5774154570493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Adverse events</topic><topic>Amylin</topic><topic>Anti-Obesity Agents - administration & dosage</topic><topic>Anti-Obesity Agents - pharmacokinetics</topic><topic>Anti-Obesity Agents - pharmacology</topic><topic>Antidiabetics</topic><topic>Arthritis</topic><topic>Asthma</topic><topic>Cardiovascular disease</topic><topic>Clinical trials</topic><topic>Diabetes</topic><topic>Dosage</topic><topic>Double-Blind Method</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Exposure</topic><topic>Female</topic><topic>Gastrointestinal diseases</topic><topic>Glucagon</topic><topic>Glucagon-like peptide 1</topic><topic>Glucagon-Like Peptides - administration & dosage</topic><topic>Glucagon-Like Peptides - pharmacokinetics</topic><topic>Glucagon-Like Peptides - pharmacology</topic><topic>Half-life</topic><topic>Hormones</topic><topic>Humans</topic><topic>Injections</topic><topic>Investigations</topic><topic>Islet Amyloid Polypeptide - administration & dosage</topic><topic>Islet Amyloid Polypeptide - adverse effects</topic><topic>Islet Amyloid Polypeptide - pharmacokinetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Obesity</topic><topic>Obesity - drug therapy</topic><topic>Osteoarthritis</topic><topic>Overweight</topic><topic>Parameters</topic><topic>Peptides</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Placebos</topic><topic>Safety</topic><topic>Weight</topic><topic>Weight control</topic><topic>Weight Loss - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Enebo, Lone B</creatorcontrib><creatorcontrib>Berthelsen, Kasper K</creatorcontrib><creatorcontrib>Kankam, Martin</creatorcontrib><creatorcontrib>Lund, Michael T</creatorcontrib><creatorcontrib>Rubino, Domenica M</creatorcontrib><creatorcontrib>Satylganova, Altynai</creatorcontrib><creatorcontrib>Lau, David C W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE 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Basic</collection><collection>SIRS Editorial</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Enebo, Lone B</au><au>Berthelsen, Kasper K</au><au>Kankam, Martin</au><au>Lund, Michael T</au><au>Rubino, Domenica M</au><au>Satylganova, Altynai</au><au>Lau, David C W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2021-05-08</date><risdate>2021</risdate><volume>397</volume><issue>10286</issue><spage>1736</spage><epage>1748</epage><pages>1736-1748</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><abstract>Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.
In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18–55 years with a body-mass index 27·0−39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0–168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete.
Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16–4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0–168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16–4·5 mg. AUC0–168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16−4·5 mg had a half-life of 159–195 h, with a median tmax of 24–72 h. Semaglutide 2·4 mg had a half-life of 145–165 h, with a median tmax of 12–24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1–5; estimated treatment difference of −6·0% [95% CI −9·9 to −2·0] for cagrilintide 1·2 mg and −7·4% [−11·2 to −3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference −7·4% [−12·8 to −2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups.
Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination.
Novo Nordisk A/S.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33894838</pmid><doi>10.1016/S0140-6736(21)00845-X</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2021-05, Vol.397 (10286), p.1736-1748 |
| issn | 0140-6736 1474-547X |
| language | eng |
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| subjects | Adult Adverse events Amylin Anti-Obesity Agents - administration & dosage Anti-Obesity Agents - pharmacokinetics Anti-Obesity Agents - pharmacology Antidiabetics Arthritis Asthma Cardiovascular disease Clinical trials Diabetes Dosage Double-Blind Method Drug dosages Drug therapy Drug Therapy, Combination Exposure Female Gastrointestinal diseases Glucagon Glucagon-like peptide 1 Glucagon-Like Peptides - administration & dosage Glucagon-Like Peptides - pharmacokinetics Glucagon-Like Peptides - pharmacology Half-life Hormones Humans Injections Investigations Islet Amyloid Polypeptide - administration & dosage Islet Amyloid Polypeptide - adverse effects Islet Amyloid Polypeptide - pharmacokinetics Male Middle Aged Obesity Obesity - drug therapy Osteoarthritis Overweight Parameters Peptides Pharmacodynamics Pharmacokinetics Pharmacology Placebos Safety Weight Weight control Weight Loss - drug effects |
| title | Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial |
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