Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.

BACKGROUND: Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide is a long-acting amylin analogue under investigation for weight management. We assessed the dose-response relationship of cagrilintide regarding the effects on bodyweight, safety, and tolerability. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial at 57 sites including hospitals, specialist clinics, and primary care centres in ten countries (Canada, Denmark, Finland, Ireland, Japan, Poland, Serbia, South Africa, the UK, and the USA). Eligible participants were adults aged at least 18 years without diabetes, with a body-mass index of at least 30 kg/m2 or at least 27 kg/m2 with hypertension or dyslipidaemia. Participants were randomly assigned (6:1) to subcutaneous self-injections of once-weekly cagrilintide (0·3, 0·6, 1·2, 2·4, or 4·5 mg), once-daily liraglutide 3·0 mg, or volume-matched placebo (for six placebo groups). The trial had a 26-week treatment period, including a dose-escalation period of up to 6 weeks, and a 6-week follow-up period without treatment. Participants and investigators were masked to the assigned study treatment with respect to active versus pooled placebo treatment, but not to different active treatments. The primary endpoint was the percentage change in bodyweight from baseline to week 26, assessed in all randomly assigned participants according to the trial product estimand (assuming all participants were adherent to treatment) and to the treatment policy estimand (regardless of adherence to treatment). Safety was assessed in all participants who received at least one dose of randomised treatment. This trial is registered with ClinicalTrials.gov, NCT03856047, and is closed to new participants. FINDINGS: Between March 1 and Aug 19, 2019, we randomly assigned 706 participants to cagrilintide 0·3-4·5 mg (100-102 per dose group), 99 to liraglutide 3·0 mg, and 101 to placebo. Permanent treatment discontinuation (n=73 [10%]) occurred similarly across treatment groups, mostly due to adverse events (n=30 [4%]). In total, 29 participants (4%) withdrew from the trial. According to the trial product estimand, mean percentage weight reductions from baseline were greater with all doses of cagrilintide (0·3-4·5 mg, 6·0%-10·8% [6·4-11·5 kg]) versus placebo (3·0% [3·3 kg]; estimated treatment difference range 3·0%-7·8%; p<0·001). Weight reductions were also greater with cagrilintide 4·5 mg versus liraglutide 3·0 mg (10·8% [11·5 kg] vs 9·0% [9·6 kg]; estimated treatment difference 1·8%, p=0·03). Similar weight loss reductions were observed with the treatment policy estimand. The most frequent adverse events were gastrointestinal disorders (eg, nausea, constipation, and diarrhoea) and administration-site reactions. More participants receiving cagrilintide 0·3-4·5 mg had gastrointestinal adverse events compared with placebo (41%-63% vs 32%), primarily nausea (20%-47% vs 18%). INTERPRETATION: Treatment with cagrilintide in people with overweight and obesity led to significant reductions in bodyweight and was well tolerated. The findings support the development of molecules with novel mechanisms of action for weight management. FUNDING: Novo Nordisk A/S.

Obesity, cardiovascular risk and healthcare resource utilization in the UK.

AIMS: Obesity and cardiovascular diseases (CVDs) often co-occur, likely increasing the intensity of healthcare resource utilization (HCRU). This retrospective, observational database study examined the joint effect of obesity and cardiovascular risk status on HCRU and compared HCRU between body mass index (BMI) categories and CVD-risk categories in the UK. METHODS: Patient demographics and data on CVD and BMI were obtained from the UK Clinical Practice Research Datalink. Cardiovascular risk status, calculated using the Framingham Risk Equation, was used to categorize people into high-risk and low-risk groups, while a CVD diagnosis was used to define the established CVD group. Patients were split into BMI categories using the standard World Health Organization classifications. For each CVD and BMI category, mean number and costs of general practitioner contacts, hospital admissions and prescriptions were estimated. RESULTS: The final study population included 1,600,709 patients. Data on CVD status were available on just over one-quarter of the sample (28.6%) and BMI data for just less than half (43.2%). The number of general practitioner contacts and prescriptions increased with increasing BMI category for each of the three CVD-risk groups. The group with established CVD had the greatest utilization of all components of healthcare resource, followed by high CVD risk then low CVD-risk groups. CONCLUSION: Increasing BMI category and CVD-risk status both affected several HCRU components. These findings highlight the importance of timely obesity management and treatment of CVD-risk factors as a means of preventing increasing HCRU.

Body mass index and risk of obesity-related conditions in a cohort of 2.9 million people: Evidence from a UK primary care database.

OBJECTIVE: Obesity rates in the United Kingdom are some of the highest in Western Europe, with considerable clinical and societal impacts. Obesity is associated with type 2 diabetes (T2D), osteoarthritis, cardiovascular disease, and increased mortality; however, relatively few studies have examined the occurrence of multiple obesity-related outcomes in the same patient population. This study was designed to examine the associations between body mass index (BMI) and a broad range of obesity-related conditions in the same large cohort from a UK-representative primary care database. METHODS: Demographic data and diagnosis codes were extracted from the Clinical Practice Research Datalink GOLD database in January 2019. Adults registered for ≥ 3 years were grouped by BMI, with BMI 18.5-24.9 kg/m2 as reference group. Associations between BMI and 12 obesity-related outcomes were estimated using Cox proportional hazard models, adjusted for age, sex, and smoking. RESULTS: More than 2.9 million individuals were included in the analyses and were followed up for occurrence of relevant outcomes for a median of 11.4 years during the study period. Generally, there was a stepwise increase in risk of all outcomes with higher BMI. Individuals with BMI 40.0-45.0 kg/m2 were at particularly high risk of sleep apnea (hazard ratio [95% confidence interval] vs. reference group: 19.8 [18.9-20.8]), T2D (12.4 [12.1-12.7]), heart failure (3.46 [3.35-3.57]), and hypertension (3.21 [3.15-3.26]). CONCLUSIONS: This study substantiates evidence linking higher BMI to higher risk of a range of serious health conditions, in a large, representative UK cohort. By focusing on obesity-related conditions, this demonstrates the wider clinical impact and the healthcare burden of obesity, and highlights the vital importance of management, treatment approaches, and public health programs to mitigate the impact of this disease.

Body mass index trajectories among people with obesity and association with mortality: Evidence from a large Israeli database.

OBJECTIVE: Previous studies using longitudinal weight data to characterize obesity are based on populations of limited size and mostly include individuals of all body mass index (BMI) levels, without focusing on weight changes among people with obesity. This study aimed to identify BMI trajectories over 5 years in a large population with obesity, and to determine the trajectories' association with mortality. METHODS: For inclusion, individuals aged 30-74 years at index date (1 January 2013) with continuous membership in Clalit Health Services from 2008 to 2012 were required to have ≥1 BMI measurement per year in ≥3 calendar years during this period, of which at least one was ≥30 kg/m2. Latent class analysis was used to generate BMI trajectories over 5 years (2008-2012). Cox proportional hazards models were used to assess the association between BMI trajectories and all-cause mortality during follow-up (2013-2017). RESULTS: In total, 367,141 individuals met all inclusion criteria. Mean age was 57.2 years; 41% were men. The optimal model was a quadratic model with four classes of BMI clusters. Most individuals (90.0%) had stable high BMI over time. Individuals in this cluster had significantly lower mortality than individuals in the other trajectory clusters (p < 0.01), including clusters of people with dynamic weight trajectories. CONCLUSIONS: The results of the current study show that people with stable high weight had the lowest mortality of all four BMI trajectories identified. These findings help to expand the scientific understanding of the impact that weight trajectories have on health outcomes, while demonstrating the challenges of discerning the cumulative effects of obesity and weight change, and suggest that dynamic historical measures of BMI should be considered when assessing patients' future risk of obesity-related morbidity and mortality, and when choosing a treatment strategy.

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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Novo Nordisk A/S.

Weight loss and risk reduction of obesity-related outcomes in 0.5 million people: evidence from a UK primary care database.

High body mass index (BMI) is known to be associated with various conditions, including type 2 diabetes (T2D), osteoarthritis, cardiovascular disease (CVD) and sleep apnoea; however, the impact of intentional weight loss on the risk of these and other outcomes is not well quantified. We examined the effect of weight loss on ten selected outcomes in a population from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Included individuals were >18 years old at the index date (first BMI value between January 2001 and December 2010). They were categorised by their weight pattern between year 1 post-index and year 4 post-index (baseline period) as having stable weight (-5% to +5%) or weight loss (-25% to -10%, plus evidence of intervention or dietary advice to confirm intention to lose weight). For inclusion, individuals also required a BMI of 25.0-50.0 kg/m2 at the start of the follow-up period, during which the occurrence of ten obesity-related outcomes was recorded. Cox proportional hazard models adjusted for BMI, comorbidities, age, sex and smoking status were used to estimate relative risks for weight loss compared with stable weight. Individuals in the weight-loss cohort had median 13% weight loss. Assuming a BMI of 40 kg/m2 before weight loss, this resulted in risk reductions for T2D (41%), sleep apnoea (40%), hypertension (22%), dyslipidaemia (19%) and asthma (18%). Furthermore, weight loss was associated with additional benefits, with lower risk of T2D, chronic kidney disease, hypertension and dyslipidaemia compared with maintaining the corresponding stable lower BMI throughout the study. This study provides objective, real-world quantification of the effects of weight loss on selected outcomes, with the greatest benefits observed for the established CVD risk factors T2D, hypertension and dyslipidaemia.

Estimating and reporting treatment effects in clinical trials for weight management: using estimands to interpret effects of intercurrent events and missing data.

In the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity.

A comprehensive descriptive assessment of obesity related chronic morbidity and estimated annual cost burden from a population-based electronic health record database.

BACKGROUND: The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions. METHODS: This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps. RESULTS: Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25-29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5- < 25 kg/m2 (5 and 9%, respectively). Healthcare costs were 1·72 times higher among men aged 25-29 with class III obesity and 2·75 times among women aged 25-29 with class III obesity compared to those of healthy weight. CONCLUSIONS: The detailed analysis describes the uneven distribution of burdens across BMI groups, age, and sex allowing policy makers to identify sub-populations for targeted interventions.

Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial.

OBJECTIVE: Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.0 mg versus placebo on weight loss in this population. RESEARCH DESIGN AND METHODS: Satiety and Clinical Adiposity-Liraglutide Evidence (SCALE) Insulin was a 56-week, randomized, double-blind, placebo-controlled, multinational, multicenter trial in individuals with overweight or obesity and type 2 diabetes treated with basal insulin and ≤2 oral antidiabetic drugs. RESULTS: Individuals were randomized to liraglutide 3.0 mg (n = 198) or placebo (n = 198), combined with intensive behavioral therapy (IBT). At 56 weeks, mean weight change was -5.8% for liraglutide 3.0 mg versus -1.5% with placebo (estimated treatment difference -4.3% [95% CI -5.5; -3.2]; P < 0.0001). With liraglutide 3.0 mg, 51.8% of individuals achieved ≥5% weight loss versus 24.0% with placebo (odds ratio 3.41 [95% CI 2.19; 5.31]; P < 0.0001). Liraglutide 3.0 mg was associated with significantly greater reductions in mean HbA1c and mean daytime glucose values and less need for insulin versus placebo, despite a treat-to-glycemic-target protocol. More hypoglycemic events were observed with placebo than liraglutide 3.0 mg. No new safety or tolerability issues were observed. CONCLUSIONS: In individuals with overweight or obesity and insulin-treated type 2 diabetes, liraglutide 3.0 mg as an adjunct to IBT was superior to placebo regarding weight loss and improved glycemic control despite lower doses of basal insulin and without increases in hypoglycemic events.

Электронные панели в первичной медико-санитарной помощи: расширение профилактики и ведения неинфекционных заболеваний на уровне первичной медико-санитарной помощи в Хорватии

В 2014 году Хорватский фонд медицинского страхования внедрил «электронные панели ПМСП для НИЗ», - инновационный инструмент, позволяющий осуществлять систематическую запись и управление данными о пациентах с неинфекционными заболеваниями (НИЗ) и их факторах риска на уровне первичной медико-санитарной помощи (ПМСП). Панели предназначены для улучшения модели лечения НИЗ на уровне ПМСП путем усиления роли врачей общей практики (ВОП) в качестве координаторов лечения пациентов с НИЗ или рисками НИЗ. Систематический и легкий доступ к важной информации стал подспорьем в принятии клинических и управленческих решений. Спустя три года после общенационального внедрения панелей ПМСП, к настоящему моменту их охват достиг 3.8 миллионов взрослых. Использование панелей привело к повышению удовлетворенности пациентов, улучшению ведения НИЗ на уровне ПМСП, сокращению числа вторичных осложнений от НИЗ, и уменьшению числа пациентов, которым необходима консультация специалиста.

Улучшение показателей по неинфекционным заболеваниям: барьеры и возможности систем здравоохранения: Казахстан

Уровень преждевременной смертности от неинфекционных заболеваний (НИЗ) в Казахстане – одиниз наиболее высоких среди стран Европейского региона ВОЗ; в 2012 г. он составил 648,31 на 100 000человек населения в возрасте от 30 до 69 лет. Значительные социально-экономические последствияэтой ситуации для развития страны обусловливают необходимость срочного укрепления потенциаласистемы здравоохранения для эффективного реагирования на растущее бремя НИЗ. В Казахстанев этом направлении уже достигнут значительный прогресс, имеется также прочная политическаяприверженность, однако показатели по контролю НИЗ все еще нуждаются в улучшении. В настоящемдокладе приведен обзор проблем и возможностей системы здравоохранения Казахстана применительнок наращиванию основных услуг профилактики, ранней диагностики и лечения НИЗ. Также освещеныпримеры передовой практики в оказании помощи пациентам с инсультом, онлайновом использованиимедицинской информации и ведении регистров. По результатам оценки сформулированы рекомендациидля дальнейших действий.

Better noncommunicable disease outcomes: challenges and opportunities for health systems. Kazakhstan country assessment

Kazakhstan has one of the highest rates of premature mortality due to noncommunicable diseases (NCDs) in the WHO European Region: the rate in 2012 was 648.31 per 100 000 population aged 30–69 years. This has signifi cant socioeconomic consequences for the development of the country and calls for immediate strengthening of the health system to respond to the growing burden of NCDs. Despite signifi cant progress and political commitment in Kazakhstan, the outcomes of NCDs could still be improved. This report reviews the challenges and opportunities of the health system in Kazakhstan for scaling up core services for the prevention, early diagnosis and management of NCDs. The report also provides examples of good practice in the care of stroke patients and online health information and registries. Policy recommendations are made for further action, based on the assessment.

Primary care electronic panels in Croatia: an information solution for more proactive primary health care services: good practice brief

In 2014, the Croatian Health Insurance Fund introduced “primary care panels for NCDs”, an innovative instrument that allows systematic recording and management of data on patients with noncommunicable diseases (NCDs). The aim of the panels was to improve model of care for NCDs in primary care by strengthening the role of general practitioners as the primary information holders and care coordinators. Systematic, easy access to important information facilitated both clinical and managerial decision-making. Three years since country-wide introduction of primary care panels, their coverage is now 3.8 million adults. They have resulted in better patient stratification, better management of NCDs in primary care, fewer secondary complications from NCDs and fewer patients who require a consultation with a specialist.

Better noncommunicable disease outcomes: challenges and opportunities for health systems: Croatia country assessment: focus on cardiovascular diseases and diabetes

In Croatia, noncommunicable diseases (NCDs) account for 93% of all deaths. They aff ect mainly the populationof working age, with an 18% probability of premature mortality from four leading NCDs. This has signifi cantsocioeconomic consequences on the development of the country, indicating that immediate action must betaken to strengthen the capacity of the health system to respond. Much progress has been made, with politicalcommitment to health reform; however, NCDs were targeted only recently. The assessment reported here,conducted by the WHO Regional Offi ce for Europe in collaboration with the Ministry of Health, will form thebasis for integrated approaches to addressing the burden of cardiovascular diseases and diabetes in Croatia. Theauthors analysed the current capacity of the health system to prevent and control these NCDs and identifi edmajor health system challenges; the document also reports good practice in using information technology forintegrating patient information. On the basis of the assessment, recommendations are made for further policiesand action.

Prevalence of depression in adults with type 2 diabetes in the Basque Country: relationship with glycaemic control and health care costs.

BACKGROUND: The aim of the study was to estimate the prevalence of depression in the population diagnosed with diabetes type 2 and to test the hypothesis that the presence of depression in such cases was associated with a) worse glycaemic control, and b) higher healthcare costs. METHODS: We conducted a cross-sectional analysis, from 1st September 2010 to 31st August 2011, among patients with type 2 diabetes aged 35 years and over in the Basque Country. It was identified how many of them had also depression. The database included administrative individual level information on age, sex, healthcare costs, other comorbidities, and values of glycaemic control (HbA1c). Deprivation index variable was used as socioeconomic measure and, to observe the coexistent pathologies, all the patients diagnoses were categorized by Adjusted Clinical Groups. We used a measure of association, a logistic and a linear regression for analysis. RESULTS: 12.392 (9.8%) of type 2 diabetes patients were diagnosed with depression, being the prevalence 5.2% for males and 15.1% for females. This comorbidity was higher among the most deprived population. There was no association between the presence of depression and glycaemic control. We estimated that the comorbidity average cost per patient/year was 516€ higher than in patients with just type 2 diabetes (P < 0.001) adjusted by the other covariates. CONCLUSIONS: We did not find any relationship between depression and glycaemic control in patients with type 2 diabetes. However, the comorbidity was associated with significantly high healthcare costs compared to that of type 2 diabetes occurring alone, after adjusting by other illness. Thus, there is a need of more precise recognition, screening and monitoring of depression among diabetic population. Evidence-based treatment for depression should be included in type 2 diabetes clinical guidelines.