QJM Advance Access originally published online on June 12, 2007
QJM 2007 100(7):395-404; doi:10.1093/qjmed/hcm044
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Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review
From Human Nutrition, Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK
Address correspondence to W.S. Leslie, Human Nutrition, Division of Developmental Medicine, University of Glasgow, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow G31 2ER. email: w.s.leslie{at}clinmed.gla.ac.uk
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Summary |
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Several drugs, or categories of drugs, listed by the WHO and other writers and used in the treatment of chronic disease, are consistently associated with weight gain as a side effect and considered ‘obesogenic’. The extent to which they may contribute to the multifactorial process behind obesity is not well documented. We systematically reviewed papers from Medline 1966–2004, Embase 1980–2004, PsycINFO 1967–2004, and Cochrane Register of Controlled Trials, to determine the effect on body weight of some drugs that are believed to favour weight gain. We included randomized controlled studies of adult participants (>18 years) prescribed a drug considered obesogenic, that compared the ‘obesogenic’ drug with placebo, an alternative drug or other treatment, and that had a duration of at least 3 months: 43 studies totalling 25 663 subjects met these criteria. The main objective of the majority of studies was to compare the efficacy and safety of drug therapy, with weight change recorded under safety outcomes; weight change was a primary outcome measure in only six studies. There was evidence of weight gain for all drugs included, up to 10 kg at 52 weeks. Differences in dosage, patient population, duration of treatment and dietary advice make generalization of the results difficult. Data on body weight are often not recorded in published clinical trials or is reported in insufficient detail. This side-effect has potentially serious consequences, and should be mentioned to patients. Weight management measures should be routinely considered when prescribing drugs known to promote weight gain. Future clinical trials should always document weight changes.
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Introduction |
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Obesity continues to increase in prevalence.1–3 In the UK, around half of women and two-thirds of men are overweight or obese.4,5 Recent Scottish data show that the figure for women has risen to 60%.6 In addition to being a major health problem in its own right, obesity is associated with a range of serious symptoms and co-morbid conditions. The estimated cost to the UK Health Service of obesity and related conditions at present is immense.5,7 If the rise in obesity continues, it is thought that by the year 2010 one third of all adults in the UK will be obese,8 and the costs to health care services will rise to an estimated £3.6 billion.5
Obesity is a consequence of energy imbalance, when energy intake exceeds energy expenditure over a prolonged period of time. Social and environmental forces have a powerful influence over energy intake and expenditure, and individuals vary in their susceptibility to these influences due to genetic and biological factors. It is the interaction of all these elements that gives rise to obesity.3 Many prescription drugs in current use are associated with weight changes. For some (e.g. certain serotonin reuptake inhibitors, oral contraceptives), the evidence of an effect on body weight is less consistent,9 while others are consistently associated with weight gain, and are considered obesogenic3,10–12 (Table 1). This effect can arise as a consequence of differing mechanisms, such as increased appetite (corticosteroids) or reduced metabolic rate (beta-adrenoceptor blockers).11 For some drugs, weight loss may have occurred as a result of the underlying disease and recovery on effective treatment will include weight regain, which would not be considered an adverse effect. However, in many cases, weight gain is an unwanted side-effect. These drugs are used in the management of chronic disease and therefore prescribed on a long-term basis. In previous research, 9% of adults attributed weight gain to drugs they were prescribed.13
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The development of obesity is a long-term multifactorial process in which obesogenic drugs play a contributory role. This review quantifies the adverse effects on body weight of those drugs that are consistently reported as obesogenic, and that are used in the treatment of chronic disease (Table 1).
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Methods |
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We electronically searched Medline 1966–2004, Embase 1980–2004, PsycINFO 1967–2004, and the Cochrane Register of Controlled Trials. The drug name or drug category was the primary key word for each search. This was mapped to relevant subheadings. The second keyword search used the terms ‘weight adj2 gain’ or ‘weight adj2 change’. Primary and secondary searches were then combined and limited to human, English language, adults, clinical trial, randomized controlled trial or controlled clinical trial. Reference lists of all relevant papers were checked. We did not hand-search journals or search the ‘grey’ literature as part of this review.
Selection of studies
Articles were selected on the basis of title and abstract. Studies were included according to the following eligibility criteria: only randomized controlled studies; adult participants (>18 years) prescribed a drug considered obesogenic; duration 
3 months; comparison of the ‘obesogenic’ drug with placebo, an alternative drug or other treatment. Outcome measures had to include measured weight change, reported quantitatively. Studies that primarily investigated the use/effect of a combination of ‘obesogenic’ drugs were excluded, as were studies in which body weight was self-reported. Studies where the drug was used to treat diseases characterized by weight loss (e.g. type 1 diabetes) were also excluded.
Quality assessment
Two reviewers checked independently that the studies identified by the search strategy met the inclusion criteria, and assessed the methodological quality of the included studies. Quality assessment focussed on the adequacy of the randomization procedure.14 As the identified studies involved different populations, drugs and dosages, no quantitative meta-analyses were done.
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Results |
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A total of 628 titles and abstracts were reviewed, and 139 publications were retrieved and reviewed in greater detail. From these, 43 studies (total 25 663 subjects) were identified that met our inclusion criteria. The main reasons for exclusion were: study duration <12 weeks; non-randomized study design; weight gain not reported or not quantified (Figure 1).
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Valproate
All four studies compared valproate with an alternative drug; no placebo-controlled studies were identified. Comparison was made with olanzapine in the treatment of bipolar disorder15 and acute mania.16 The objective of both these studies was to compare the drugs in terms of efficacy and safety. Biton et al.17 compared valproate with lamotrigine in patients with epilepsy. The aim of the fourth study18 was to determine the efficacy and safety of topiramate, in comparison with cabamazepine and valproate monotherapy, in the initial treatment of newly diagnosed epilepsy.
Weight change was the primary outcome measure in only one study,17 and a secondary measure to assess safety in the remaining studies. The mean dosage of valproate differed in each study (Table 2).
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Lithium
Only one study fulfilled the inclusion criteria and compared lithium with carbamazepine as a prophylactic agent in bipolar disorder.19 The main outcome measure was relapse, with weight gain recorded as an assessment of side-effects. The initial dose of lithium was 400 mg twice daily.
Atypical antipsychotics
In three studies, olanzapine was compared with placebo in the treatment of alcohol dependence disorder,20 and borderline personality disorder.20,21 Ziprasidone was compared with placebo in the treatment of schizophrenia.23 In the remaining studies, comparisons were made between an atypical antipsychotic and an alternative drug: clozapine, olanzapine, and risperidone vs. haloperidol,24 olanzapine vs. sodium valproate,15,16 olanzapine vs. haloperidol,25,26 risperidone vs. amilsulpride,27 clozapine vs. chlorpromazine,28 olanzapine vs. aripiprazole29 and olanzapine vs. amisulpride.30
Only two studies24,29 specifically examined weight change as a primary outcome; in the remainder of the studies, clinical response was the primary outcome with weight change recorded as a means of assessing safety.
Corticosteroids
Only one randomized controlled trial was identified,31 comparing prednisone with radiotherapy in the treatment of Graves’ ophthalmopathy. The objective of the study was to compare the efficacy and tolerability of the treatments: clinical response was the primary outcome measure, with weight change recorded as a side-effect.
Insulin
The studies included were restricted to the treatment of type 2 diabetes. In all studies, insulin therapy alone was compared with either oral agents32–34 or with insulin plus oral agents.35–37 The dosage of insulin varied in each study, and was calculated according to the participant's body weight, subsequently adjusted according to blood glucose results.
Sulphonylureas
Treatment with a sulphonylurea was compared with placebo alone in two studies,38,39 with another oral hypoglycaemic agent and placebo in two studies,40,41 with insulin in two studies,32,34 and with an alternative oral hypoglycaemic agent in three studies.42,43,48 Weight change was a primary outcome measure in only one study.42 In the UKPDS study, the main objective was to determine the risk of micro or macro-vascular complications, with weight change recorded under adverse events. The objective of the remaining studies was to determine efficacy, safety and tolerability, with clinical response as the primary outcome measure and weight change recorded under safety outcomes.
Thiazolidinediones
Three studies compared a thiazolidinedione with placebo in type 2 diabetic patients. Patel et al.44 assessed the metabolic effects of four doses of rosiglitazone, Iwamoto et al. 45 investigated the efficacy and safety of troglitazone and Wallace et al.46 examined the effect of pioglitazone on beta cell function and insulin sensitivity. The metabolic effects of pioglitazone were compared with metformin in one study,47 and in the final study pioglitazone was compared with glimepiride with regard to changes in glycaemic control and insulin sensitivity.48 In all studies, weight change was a secondary outcome.
Tricyclic antidepressants
All three studies compared the efficacy and tolerability of a tricyclic antidepressant with an alternative anti-depressant: paroxitine in comparison with nortriptyline,49 bupropion compared with doxepin,50 and mirtazapine with amitryptiline and placebo.51 Weight change was the primary outcome measure in one study,49 and assessed as an adverse event in the other two. The dosage of tricyclic antidepressant was not reported in one study,49 and differed in the other two.
Beta-adrenergic blocking agents
Two studies compared the effect on lipid profiles between a chosen beta-blocker and an alternative anti-hypertensive agent: captopril vs. metoprolol52 and nifedipine vs. atenolol.53 The effect of long-term treatment with propranolol on body weight study was the main outcome in one study.54 Two studies compared treatment with a beta-blocker with bendroflumethiazide: one investigated the metabolic effects,55 the other compared the effects on mortality.56 Wilhelmsen et al.57 compared beta-blocker treatment with diuretic treatment to determine differences in the incidence of non-fatal myocardial infarction, coronary heart disease mortality and total mortality.
Cyproheptadine
No studies were identified that fulfilled the inclusion criteria.
Methodological quality of included studies
All studies included in this review were described as randomized, but in the majority (72%) the methods of randomization and concealment were not described. In one study,35 the method of randomization (consecutive and alternate) was inadequate.14 In 11 studies the method of randomization was clearly described and considered adequate. Inclusion and exclusion criteria were clearly described in all studies. Intention-to-treat analysis was used in 51% of studies.
Weight change
In the majority of studies, weight change was not a primary outcome measure, but was measured and recorded under safety outcomes; weight change was a primary outcome measure in only six studies.17,24,29,42,49,54 The effects on body weight differed greatly amongst the different categories of drugs. In the majority of studies, weight gain was the result of treatment, with some of the greatest weight gains seen in subjects prescribed anti-psychotic medications. However, weight loss was observed in some studies (Table 2).
Six studies investigated whether weight gain was dose-related. Results varied, with three studies reporting no relationship between drug dosage and weight gain.17,23,24 Some correlation was observed between dosage of insulin and weight gain.35,36 One study44 suggested that a clinically significant increase in body weight might be observed at higher doses of rosiglitazone.
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Discussion |
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Weight change occurs over time and against a background of progressive weight gain in the ‘normal’ population. There is no ideal time to examine the possible obesogenic effects of drugs. It can be assumed that most such drugs will have a most marked effect early in treatment, reaching a plateau effect by 6–12 months (although all healthy subjects are likely to continue to gain weight at around 1 kg/year).58,59
If the underlying disease for which the drug was prescribed has caused weight loss, then recovery on effective treatment will include weight regain. The primary treatment of type 1 diabetes is an obvious example. This was not considered an obesogenic effect, and such studies were excluded by our own inclusion criteria
The effect of the drug treatment on body weight was reported in all of the studies in this review, and provides evidence that weight gain is associated with some drugs, and is a major and continual burden on public health. All of the drugs included in this review are used in the treatment of chronic disease. In the UK, it is estimated that around 2.6 million people have been diagnosed with coronary heart disease,60 and beta-blockers (unless contraindicated) have a prominent role in its management.61–63 Valproate is one of the first-line treatments for epilepsy,64 and is also used in the treatment of manic episodes associated with bipolar disorder. In Scotland, around 20 000–40 000 people have active epilepsy, with about 2000–3000 new cases per year.64 In England 
380 000 people suffer from the disease (1:130 people).65 Bipolar disorder is the third most common mood disorder after major depression and schizophrenia, and affects around 1% of the population 66. Around 1.3 million people in the UK suffer from either type 1 or type 2 diabetes.60 In the light of these figures, the number of individuals in the population receiving treatment with an obesogenic drug is potentially quite high. In Scotland alone, the number of prescriptions dispensed for beta-blockers and tricyclic antidepressants between 2004 and 2005 exceeded 1 million and 2 million, respectively (Table 3) (Audrey Thompson, personal communication).
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It is generally accepted that during adult life, most people will gain weight. The rate at which weight is gained varies, but a 0.5–1 kg gain per year is considered average in the general population.58,59 In some studies in this review, weight gain in excess of this was observed over a much shorter duration: in particular, those involving anti-psychotic drugs. Olanzapine and clozapine were associated with the greatest weight gains, a finding that concurs with previous reviews in this area.67,68 The weight gains with beta-blocker therapy were relatively small, but more marked in those prescribed propranolol. Previous research has also identified propranolol as the beta-blocker most likely to cause weight gain.6970
In the UK at present, a significant proportion of the population are considered either overweight or obese,5,6 and an annual weight gain of 5 kg/year or more is not uncommon. It is therefore likely that prior to treatment with a drug known to favour weight gain, many individuals will already be overweight and struggling to avoid further gain. The additional effect of obesogenic drug therapy may tip the balance to increase BMI towards the obese category, or be sufficient to make co-morbidities clinically apparent. Given the common and long-term use of many of these drugs, it is likely that they play a significant contributory role in the increasing prevalence of obesity.
Non-compliance with any drug therapy is a widespread problem,71 and around half of patients prescribed long-term medication for the management of chronic diseases do not comply fully with treatment.72 Poor compliance with drug therapy may lead to a worsening of the underlying condition and contribute to increased health care costs.73 Non-compliance is reported as an issue with many of the drugs included in this review,73–76 and the weight gain associated with them may contribute to this. For those prescribed anti-psychotic medication, weight gain is acknowledged as a major cause of non-compliance.76 It is unclear whether this known side-effect is routinely discussed with patients prior to prescription but it should be, on medico-legal grounds. The treatment of anti-psychotic-induced weight gain is now considered a treatment priority,77 and research on approaches to address this is a growing area.77–81 It would seem greatly preferable to discuss the probability of weight gain as a side-effect, and to provide effective advice and support to avoid weight gain. For a number of the drug classes included, weight management should form an essential part of treatment for the underlying disease, e.g. in type 2 diabetes and hypertension, access to dietitians should be routine. For other drugs (notably anti-psychotics) provision of dietary advice is a new consideration.82
Study limitations
The drugs included in the present review were those consistently reported in medical/scientific literature, used in the treatment of chronic disease and believed to affect weight.3,9–12 Many other drugs prescribed today may also affect weight. Few studies included in the review examined weight change as a primary outcome, and in many instances the variability of weight change was not reported. Studies that primarily investigated the effect of a combination of ‘obesogenic’ drugs were excluded, but it was not always possible to be certain that other drugs known to favour weight gain were not also being taken. However, the process of randomization should have ensured that any such confounding effect would have been similar in all groups
Conclusions
This review provides evidence of the weight gain potential of some common drugs. It is perhaps only now, in light of the present epidemic of obesity, that the negative effect on body weight is a pertinent issue. Body weight and height are routinely recorded in virtually all clinical trials, but seldom reported. The potential of weight gain should be discussed with patients prior to the institution of therapy, both for medico-legal grounds and to ensure that weight maintenance is promoted and adhered to.
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We thank Audrey Thompson, Medicines Management Advisor, Greater Glasgow Primary Care Trust, for information on drug prescribing. Financial support was provided by Roche Products Ltd, to permit the employment of WL.
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References |
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1. Nutrition and Physical Activity Task Force of the Department of Health. Reversing the increasing problem of obesity in England. (1995) Department of Health.
2. Scottish Intercollegiate Guidelines Network. Obesity in Scotland. Integrating prevention with weight management. (1996) Edinburgh.
3. World Health Organisation. Obesity, preventing and managing the global epidemic. In: Report of a WHO consultation on obesity (1998).
4. The Scottish Executive Department of Health. The Scottish Health Survey 1998. (2000) HMSO.
5. National Audit Office. Tackling Obesity In England (2001) London: The Stationery Office Ltd.
6. The Scottish Executive Department of Health. The Scottish Health Survey 2003. (2005) HMSO.
7. Walker A. The cost of doing nothing—the economics of obesity in Scotland. (2003) Robertson Centre for Biostatistics, University of Glasgow.
8. Williams G. Obesity and type 2 diabetes: a conflict of interests. Int J Obes (1999) 23(Suppl. 7):S2–4.
9. Keith SW, Redden DT, Katzmarzyk PT, et al. Putative contributors to the secular increase in obesity: exploring the roads less travelled. Int J Obes (2006) 30:1585–94.[CrossRef][Web of Science][Medline]
10. Lean MEJ. Management of Obesity and Overweight. Medicine (1998) 26:9–13.
11. Pijl H, Meinders AE. Bodyweight change as an adverse effect of drug treatment. Drug Safety (1996) 14:329–42.[Web of Science][Medline]
12. Finer N. Clinical Assessment, Investigation and Principles of Management: Realistic Weight Goals. In: Clinical Obesity—Kopleman PG, Stock MJ, eds. (1998) London: Blackwell Science. 350–76.
13. Vossenaar M, Anderson A, Lean M, Ocke M. Perceived reasons for weight gain in adulthood. Int J Obes (2004) 28(S1):S67.
14. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD guidelines for those carrying out or commissioning reviews. In: (CRD report 4). (1996) York: NHS Centre for Reviews and Dissemination, University of York.
15. Zajecka JM, Weisler R, Sachs G, Swann AC, Wozniak P, Sommerville KW. A comparison of the efficacy and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disease. J Clin Psychiatry (2002) 63:1148–55.[Web of Science][Medline]
16. Tohen M, Ketter TA, Zarate CA, Suppes T, Frye M, Altshuler L, Zajecka JM, Schuh LM, Risser RC, Brown E, Baker RW. Olanzapine versus divalproex for the treatment of acute mania and maintenance of remission: a 47 week study. Am J Psychiatry (2003) 160:1263–71.
17. Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology (2001) 56:172–7.
18. Privitera MJ, Brodie MJ, Mattson RH, Chadwick DW, Neto W, Wang S. Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurol Scand (2003) 107:165–75.[CrossRef][Web of Science][Medline]
19. Coxhead N, Silverstone T, Cookson J. Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand (1992) 85:114–18.[Web of Science][Medline]
20. Guardia J, Segura L, Gonzalvo B, Iglesias L, Roncero C, Cardus M, Casas M. A double blind, placebo controlled study of olanzapine in the treatment of alcohol-dependence disorder. Alcohol Clin Exp Res (2004) 28:736–45.[Web of Science][Medline]
21. Bogenschutz MP, Nurnberg G. Olanzapine versus placebo in the treatment of borderline personality disorder. J Clin Psychiatry (2004) 65:104–9.[Web of Science][Medline]
22. Zanarini MC, Frankenburg FR. Olanzapine treatment of female borderline personality disorder patients: a double blind, placebo-controlled pilot study. J Clin Psychiatry (2001) 62:849–54.[Web of Science][Medline]
23. Arato M, O’Connor, Meltzer HY. A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the ziprasidone extended use in schizophrenia (ZEUS) study. Int Clin Psychopharmacol (2002) 17:207–15.[CrossRef][Web of Science][Medline]
24. Czobor P, Volavka J, Sheitman B, Lindenmayer JP, Citrome L, Mcevoy J, Cooper TB, Chakos M, Lieberman JA. Antipsychotic-induced weight gain and therapeutic response: A differential association. J Clin Psychopharmacol (2002) 22:244–51.[CrossRef][Web of Science][Medline]
25. Tran PV, Tollefson G, Gary D, Sanger TM, Lu Y, Berg PH, Beasley CM Jr. Olanzapine versus haloperidol in the treatment of schizoaffective disorder: Acute and long term therapy. Br J Psychiat (1999) 174:15–22.
26. Lieberman JA, Tollefson G, Tohen M, Green A, Gu RE, Kahn R, Mc Evoy J, Perkins D, Sharma T, Zipursky R, Wei H, Hamer R. Comparative efficacy and safety of atypical and conventional antipsychotice drugs in first-episode psychosis: A randomised, double blind trial of olanzapine versus haloperidol. Am J Psychiatry (2003) 160:1396–404.
27. Sechter D, Peuskins J, Fleuot O, Rein W, Lecrubier Y. Amisupride vs, Risperidone in chronic schizophrenia: results of a 6-month double-blind study. Neuropsychopharmacology (2002) 27:1071–81.[CrossRef][Web of Science][Medline]
28. Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, Ji Z, Koch G, Hamer R. Atypical and conventional antipsychotic drugs in treatment-naïve first-episode schizophrenia: a 52-week randomised trial of clozapine Vs chlorpromazine. Neuropsychopharmacology (2003) 28:995–1003.[Web of Science][Medline]
29. McQuade RD, Sotck E, Marcus R, Jody D, Gharbia NA, Vanveggel S, Archibald D, Carson WH. A comparison of weight change during treatment with olanzapine of aripiprazole: Results from a randomised double-blind study. J Clin Psychiatry (2004) 65:47–56.[Web of Science][Medline]
30. Mortimer A, Martin S, Loo H, Peuskens J. A double-blind randomised comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia. Int Clin Psychopharmacol (2004) 19:63–9.[CrossRef][Web of Science][Medline]
31. Prummel MF, Mourits MP, Blank L, Berghout A, Koorneef L, Wiersinga WM. Randomised double-blind trial of prednisone versus radiotherapy in Graves’ ophthalmopathy. Lancet (1993) 342:949–54.[CrossRef][Web of Science][Medline]
32. Nathan DM, Roussell A, Godine JE. Glyburide or insulin for metabolic control in non-insulin dependent diabetes. Ann Intern Med (1998) 108:334–40.
33. Tovi J, Theoblad H, Engfeldt P. Effect of metabolic control on 24-hour ambulatory blood pressure in elderly non-insulin-dependent diabetic patients. J Hum Hypertens (1996) 10:589–94.[Web of Science][Medline]
34. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet (1998) 352:837–53.[CrossRef][Web of Science][Medline]
35. Chow CC, Sorensen JP, Tsang LWW, Cockram CS. Comparison of insulin with or without continuation of oral hypoglycaemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care (1995) 18:307–14.[Abstract]
36. Yki-Jarvinen H, Kauppila M, Kujansu E, et al. Comparison of insulin regimes in patients with non-insulin dependent diabetes mellitus. N Engl J Med (1992) 327:1426–33.[Abstract]
37. Yki-Jarvinen H, Ryys L, Kauppila M, et al. Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab (1997) 82:4037–43.
38. Simonson DC, Kourides IA, Feinglos M, Shamoon H, Fischette CT. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycaemic control and insulin secretion in NIDDM: Results of two multicenter, randomised, placebo-controlled trials. Diabetes Care (1997) 20:597–606.[Abstract]
39. Bautista JL, Bugos C, Dirnberger G, Atherton T. Efficacy and safety profile of Glimepiride in Mexican American patients with Type 2 diabetes mellitus: A randomised placebo-controlled study. Clin Ther (2003) 25:194–209.[CrossRef][Web of Science][Medline]
40. Segal P, Feig P, Schernthaner G, Ratzmann KP, Rybka J, Petzinna D, Berlin C. The efficacy and safety of miglitol therapy compared with glibenclimide in patients with NIDDM inadequately controlled by diet alone. Diabetes Care (1997) 20:687–91.[Abstract]
41. Johnstone PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of 
-Glocoside inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocinol Metab (1998) 83:1515–22.
42. Campbell IW, Menzies DG, Chalmers J, McBain AM, Brown IRF. One year comparative trial of metformin and glipizide in type 2 diabetes mellitus. Diabet Metab (1994) 20:394–400.[Web of Science][Medline]
43. Marbury T, Huang WC, Strange P, Lebovitz H. Repaglinide versus glyburide: a one-year comparison trial. Diabetes Res Clinical Pract (1999) 43:155–66.[CrossRef]
44. Patel J, Anderson RJ, Rappaport EB. Rosiglitazone monotherapy improves glycaemic control in patients with type2 diabetes: a twelve-week, randomised, placebo-controlled study. Diabetes Obes Metab (1999) 1:165–72.[CrossRef][Web of Science][Medline]
45. Iwamoto Y, Kosaka K, Kuzuya T, Akanuma Y, Shigeta Y, Kaneko T. Effects of troglitizone: A new hypoglycaemic agent in patients with NIDDM poorly controlled by diet. Diabetes Care (1996) 19:151–6.[Abstract]
46. Wallace TM, Levy JC, Matthews DR. An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazones in a placebo-controlled randomised study. Diabet Med (2004) 21:568–76.[CrossRef][Web of Science][Medline]
47. Schernthaner G, Matthews DR, Charbonnel B, Hanefield M, Brunetti P. Efficacy and safety of Pioglitazone versus metformin in patients with type 2 diabetes mellitus: A double-blind randomised trial. J Clin Endocrinol Metab (2004) 89:6068–76.
48. Tan M, Johns D, Gonzalez G, Antunez O, Fabian G, Flores-Lozano F, Guajardo SZ, Garz E, Morales H, Konkoy C, Herz M. Effects of pioglitazone and glimepiride on glycaemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: A multicentre, randomised, double-blind, parallel-group trial. Clin Ther (2004) 26:680–693.[CrossRef][Web of Science][Medline]
49. Weber E, Stack J, Pollock BG, Mulsant B, Begley A, Mazunder S, Reynolds CF. Weight change in older depressed patients during acute pharmocotherapy with paroxetine and nortriptyline: A double-blind randomised trial. Am J Geriatr Psychiatry (2000) 8:245–50.[CrossRef][Web of Science][Medline]
50. Feighner J, Hendrickson G, Miller L, Stern W. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. J Clin Psychopharmacol (1986) 6:27–32.[Web of Science][Medline]
51. Montgomery SA, Reimitz P-E, Zivkov M. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. Int Clin Psychopharmacol (1998) 13:63–73.[Web of Science][Medline]
52. Foss OP, Jensen EK. The effect of captopril and metoprolol as monotherapy or combined with bendroflumethiazide on blood lipids. J Intern Med (1990) 227:119–23.[Web of Science][Medline]
53. Houston MC, Olafsson L, Burger MC. Effects of nifedipine GITS and Atenolol monotherapy on serum lipids, blood pressure, heart rate and weight in mild to moderate hypertension. Angiology (1991) 42:681–9.
54. Rossner S, Taylor CL, Byington RP, Furberg CD. Long term propranolol treatment and changes in body weight after myocardial infarction. Br Med J (1990) 300:902–3.[Web of Science][Medline]
55. Berglund G, Andersson O, Widgren B. Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic: A 10-year controlled trial with bendroflumethiazide. Acta med Scand (1986) 220:419–24.[Web of Science][Medline]
56. Wikstrand J, Warnold I, Olsson G, Tuomilehto J, Elmfeldt D, Berglund G. Primary prevention with metoprolol in patients with hypertension. JAMA (1988) 259:1976–82.
57. Wilhelmsen L, Berglund G, Elmfeldt D, Fitsimmons T, Holzgreve H, Hosie J, Hornkvist PE, Pennert K, Tuomolehto J, Wedel H. Beta-blockers versus diuretics in hypertensive men: Main results from the HAPPHY trial. J Hypertens (1987) 5:561–72.[CrossRef][Web of Science][Medline]
58. Heitmann BL, Garby L. Patterns of long-term weight changes in overweight developing Danish men and women aged between 30 and 60 years. Int J Obes (1999) 23:1074–8.[CrossRef][Web of Science][Medline]
59. Phelan S, Hill JO, Lang W, Dibello JR, Wing RR. Recovery from relapse among successful weight maintainers. Am J Clin Nutr (2003) 78:1079–84.
60. British Heart Foundation Statistics [www.heartstats.org].
61. National Institute for Clinical Excellence. Prophylaxis for patients who have suffered a myocardial infarction (2000) London: National Institute for Clinical Excellence.
62. Scottish Intercollegiate Guidelines Network. Secondary prevention of coronary heart disease following myocardial infarction (2001) Edinburgh: Scottish Intercollegiate Guidelines Network.
63. Scottish Intercollegiate Guidelines Network. Management of stable angina (2001) Edinburgh: Scottish Intercollegiate Guidelines Network.
64. Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults (2003) Edinburgh: Scottish Intercollegiate Guidelines Network.
65. Department of Health. Improving services for people with Epilepsy (2003) London: Department of Health Publications.
66. Scottish Intercollegiate Guidelines Network. Core Interventions in the treatment and management of schizophrenia in primary and secondary care (2002) London: Scottish Intercollegiate Guidelines Network.
67. Allison DB, Mentore JL, Moonseong H, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis. Am J Psychiatry (1999) 156:1686–96.
68. Ness-Abramof R, Apovian CM. Drug Induced Weight Gain. Drugs Today (2005) 8:547–55.
69. Cheskin LJ, Bartlett SJ, Zayas R, Twilley CH, Allison DB, Contoreggi C. Prescription Medications: A Modifiable Contributor to Obesity. South Med J (1999) 92:898–904.[Web of Science][Medline]
70. Sharma A, Pischon T, Hardt S, Kunz I, Luft FC. ß-Adrenergic Receptor Blockers and Weight Gain: A Systematic Analysis. Hypertension (2001) 37:250–4.
71. Wertheimer AI, Santella TM. Medication non-compliance: What we know, what we need to learn. Fabad J Pharmaceut Sci (2003) 28:207–17.
72. Perkins DO. Predictors of non-compliance in patients with schizophrenia. J Clin Psychiatry (2002) 63:1121–8.[Web of Science][Medline]
73. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med (2005) 355:487–97.
74. Hertz RP, Unger AN, Lustik MB. Adherence with pharmacotherapy for type 2 diabetes: a retrospective cohort study of adults with employer-sponsored health insurance. Clin Ther (2005) 27:1064–73.[CrossRef][Web of Science][Medline]
75. Lowry KP, Dudley TK, Oddone EZ, Bosworth HB. Intentional and unintentional non-adherence to anti-hypertensive medication. Ann Pharmacother (2005) 39:1198–203.
76. Weiden PJ, Mackell JA, McDonnell DD. Obesity as a risk for antipsychotic noncompliance. Schizophrenia Res (2004) 66:51–7.[CrossRef][Web of Science][Medline]
77. Werneke U, Taylor D, Sanders TAB, Wessely S. Behavioural management of antipsychotic-induced weight gain: a review. Acta Psychiatr Scand (2003) 108:252–9.[CrossRef][Web of Science][Medline]
78. Ohlson RI, Treasure J, Pilowsky LS. A dedicated nurse-led service for antipsychotic-induced weight gain. Psychiatric Bull (2004) 28:164–6.[CrossRef]
79. Ball MP, Coons VB, Buchanan RW. A program for treating Olanzapine-related weight gain. Psychiatric Services (2001) 52:967–9.
80. Vreeland B, Minsky S, Menza M, Radler DR, Roemheld-Hamm B, Stern R. A program for managing weight gain associated with atypical antipsychotics. Psychiatric Services (2003) 54:1155–7.
81. Littrell KH, Hilligoss NM, Kirshner CD, Petty RG, Johnson CG. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh (2003) 35:237–41.[CrossRef][Web of Science][Medline]
82. Lean MEJ, Pjonk FG. Patients on atypical antipsychotic drugs. Diabetes Care (2003) 26:1597–605.
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