Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial

CAMELLIA-TIMI 61 Steering Committee Investigators

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Abstract

Background: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. Methods: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Findings: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66–0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). Interpretation: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Funding: Eisai.

Original languageEnglish (US)
Pages (from-to)2269-2279
Number of pages11
JournalThe Lancet
Volume392
Issue number10161
DOIs
StatePublished - Nov 24 2018

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Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Prediabetic State
lorcaserin
Vascular Diseases
Hypoglycemia
Life Style
Weight Loss
Receptor, Serotonin, 5-HT2C
Weights and Measures
Serotonin Receptor Agonists
Intention to Treat Analysis
Glycosylated Hemoglobin A
Appetite
Proportional Hazards Models
Hyperglycemia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61) : a randomised, placebo-controlled trial. / CAMELLIA-TIMI 61 Steering Committee Investigators.

In: The Lancet, Vol. 392, No. 10161, 24.11.2018, p. 2269-2279.

Research output: Contribution to journalArticle

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title = "Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial",
abstract = "Background: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. Methods: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Findings: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8{\%}) had diabetes, 3991 (33·3{\%}) prediabetes, and 1193 (9·9{\%}) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95{\%} CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19{\%} in patients with prediabetes (172 [8·5{\%}] of 2015 vs 204 [10·3{\%}] of 1976; hazard ratio 0·81, 95{\%} CI 0·66–0·99; p=0·038) and by 23{\%} in patients without diabetes (174 [6·7{\%}] of 2615 vs 215 [8·4{\%}] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2{\%}] vs 151 [7·6{\%}]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33{\%} (95{\%} CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0{\%}). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4{\%}] vs four [0·1{\%}] events; p=0·054). Interpretation: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Funding: Eisai.",
author = "{CAMELLIA-TIMI 61 Steering Committee Investigators} and Bohula, {Erin A.} and Scirica, {Benjamin M.} and Inzucchi, {Silvio E.} and McGuire, {Darren K.} and Keech, {Anthony C.} and Smith, {Steven R.} and Estella Kanevsky and Murphy, {Sabina A.} and Leiter, {Lawrence A.} and Dwyer, {Jamie P.} and Ramon Corbalan and Christian Hamm and Lee Kaplan and Nicolau, {Jose Carlos} and Ophuis, {Ton Oude} and Ray, {Kausik K.} and Mikhail Ruda and Jindrich Spinar and Tushar Patel and Wenfeng Miao and Carlos Perdomo and Bruce Francis and Shobha Dhadda and Bonaca, {Marc P.} and Ruff, {Christian T.} and Sabatine, {Marc S.} and Wiviott, {Stephen D.} and Silvio Inzucchi and Anthony Keech and Andrew Satlin and Conville Brown and Andrzej Budaj and Jamie Dwyer and Armando Garcia-Castillo and Milan Gupta and {Oude Ophuis}, Ton and Kauski Ray and Neil Weissman and White, {Harvey D.} and J. Amerena and M. Arstall and D. Colquhoun and R. Jayasinghe and A. Lee and R. Lehman and R. Moses and J. Proietto and P. Purnell and J. Waites and Chang, {Alice Y}",
year = "2018",
month = "11",
day = "24",
doi = "10.1016/S0140-6736(18)32328-6",
language = "English (US)",
volume = "392",
pages = "2269--2279",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10161",

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TY - JOUR

T1 - Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61)

T2 - a randomised, placebo-controlled trial

AU - CAMELLIA-TIMI 61 Steering Committee Investigators

AU - Bohula, Erin A.

AU - Scirica, Benjamin M.

AU - Inzucchi, Silvio E.

AU - McGuire, Darren K.

AU - Keech, Anthony C.

AU - Smith, Steven R.

AU - Kanevsky, Estella

AU - Murphy, Sabina A.

AU - Leiter, Lawrence A.

AU - Dwyer, Jamie P.

AU - Corbalan, Ramon

AU - Hamm, Christian

AU - Kaplan, Lee

AU - Nicolau, Jose Carlos

AU - Ophuis, Ton Oude

AU - Ray, Kausik K.

AU - Ruda, Mikhail

AU - Spinar, Jindrich

AU - Patel, Tushar

AU - Miao, Wenfeng

AU - Perdomo, Carlos

AU - Francis, Bruce

AU - Dhadda, Shobha

AU - Bonaca, Marc P.

AU - Ruff, Christian T.

AU - Sabatine, Marc S.

AU - Wiviott, Stephen D.

AU - Inzucchi, Silvio

AU - Keech, Anthony

AU - Satlin, Andrew

AU - Brown, Conville

AU - Budaj, Andrzej

AU - Dwyer, Jamie

AU - Garcia-Castillo, Armando

AU - Gupta, Milan

AU - Oude Ophuis, Ton

AU - Ray, Kauski

AU - Weissman, Neil

AU - White, Harvey D.

AU - Amerena, J.

AU - Arstall, M.

AU - Colquhoun, D.

AU - Jayasinghe, R.

AU - Lee, A.

AU - Lehman, R.

AU - Moses, R.

AU - Proietto, J.

AU - Purnell, P.

AU - Waites, J.

AU - Chang, Alice Y

PY - 2018/11/24

Y1 - 2018/11/24

N2 - Background: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. Methods: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Findings: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66–0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). Interpretation: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Funding: Eisai.

AB - Background: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. Methods: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Findings: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66–0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). Interpretation: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Funding: Eisai.

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