Dr finds that statins do not help diabetics and official guidelines regarding statin use should be re-examined and reformulated by experts independent from the pharmaceutical industry

This paper was published in Reviews on Recent Clinical Trials 2012 May;7(2):150-7

Study title and authors:
Is the use of cholesterol-lowering drugs for the prevention of cardiovascular complications in type 2 diabetics evidence-based? A systematic review.

de Lorgeril M, Hamazaki T, Kostucki W, Okuyama H, Pavy B, McGill AT, Rabaeus M.
Laboratoire Coeur & Nutrition, Université Joseph Fourier-CNRS, Faculté de Médecine, 38706 La Tronche, France. michel.delorgeril@ujf-grenoble.fr

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22353198

This paper systematically reviewed the results of high-quality double blind trials testing whether cholesterol-lowering drugs (statins and fibrates) reduce mortality and cardiovascular complications specifically in type two diabetics.

The review of the scientific literature found four trials, three statin and one fibrate.
(a) Statin trials:
(ai) The Collaborative Atorvastatin Diabetes Study (CARDS) trial was discontinued 2 years before the anticipated end and in the absence of significant effect on both overall and cardiovascular mortality, suggesting that the trial should not have been prematurely stopped.
(aii) The Deutsche Diabetes Dialyse Studie (4D) trial showed no significant effect on heart attack, stoke or cardiovascular and overall death rates.
(aiii) The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) trial showed no significant effect in nonfatal heart attacks, nonfatal stroke, coronary artery bypass surgery, resuscitated cardiac arrest, worsening or unstable angina requiring hospitalization or cardiovascular and overall death rates.
(b) Fibrate trial: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial showed no significant effect on coronary heart disease death, non-fatal heart attack or death rates.

Dr de Lorgeril concluded: "This review does not support the use of cholesterol-lowering drugs (such as statin and fibrate) to reduce mortality and cardiovascular complications in type two diabetics. Official guidelines should be re-examined and reformulated by experts independent from the pharmaceutical industry".



In type 1 diabetics, statins significantly increase the risk of developing diabetes-related complications.

This study was published in Diabetes Research and Clinical Practice 31st October 2015

Study title and authors:
Statins are Independently Associated with Increased HbA1c in Type 1 Diabetes–The Thousand & 1 Study
Magnus Thorsten Jensen, Henrik Ullits Andersen, Peter Rossing, Jan Skov Jensen

This study can be accessed at: http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(15)00423-4/abstract

The term HbA1c refers to glycated haemoglobin. It develops when haemoglobin, a protein within red blood cells that carries oxygen throughout your body, joins with glucose in the blood, becoming 'glycated'.

By measuring glycated haemoglobin (HbA1c), clinicians are able to get an overall picture of what our average blood sugar levels have been over a period of weeks/months.

For people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications.

This study examined the association between statin use and HbA1c levels in type 1 diabetics without known heart disease. The study included 1,093 patients, average age 49.6 years, who had had type 1 diabetes for an average of 25.5 years.

The study found that statin use was independently and significantly associated with higher HbA1c levels.



Statins do not prevent cardiovascular and all-cause deaths

This paper was published in the Journal of Clinical Lipidology Volume 7, Issue 3 , Pages 222-224, May 2013
 
Study title and authors:
Point: Why statins have failed to reduce mortality in just about anybody
Eddie Vos, Colin P. Rose, Pierre Biron
127 Courser Road, Sutton, QC, Canada J0E 2K0

Department of Medicine, McGill University, Montreal, QC, Canada H3H 1V6

 

This paper can be accessed at: http://www.lipidjournal.com/article/S1933-2874(13)00052-4/abstract

 

This paper reviewed the scientific evidence regarding statins and death rates.

 

(i) In JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial), a trial involving 17,802 participants randomised to rosuvastatin or placebo found for all participants the cardiovascular mortality was not reduced.

(ii) All published trials with placebo controls conclusively establish that statins do not reduce mortality in women.

(iii) There are no mortality figures suggesting a positive effect for people taking statins for more than five or six years.

(iv) In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, in patients older than 70 years of age, there appeared to be arising increased rate of cancer, which may indicate that longer intervals of statin therapy may have other costs in the elderly.

(v) For both genders, the lack of all-cause mortality benefit is also illustrated by all published studies using atorvastatin vs. placebo, including the summary of 49 in-house studies including 14,236 individual patients.

(vi) The secondary prevention study SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) ended with five more deaths on highdose atorvastatin than on placebo.

(vii) To date, there are no placebo-controlled studies showing a mortality benefit when patients used lovastatin, fluvastatin, cerivastatin, or pitavastatin.

(viii) No mortality benefit from statins has ever been shown in patients older than 70 years of age.

(ix) No mortality benefit from statins has ever been shown in patients with heart failure.

(x) No mortality benefit from statins has ever been shown in patients with kidney failure.

(xi) Patients believing consciously or subliminally that ‘‘their cholesterol is under control’’ because they take a statin may postpone embarking on lifestyle changes, such as stopping smoking and abandoning eating habits that produce obesity and diabetes.

(xii) There is evidence that statins themselves promote diabetes, a life-long health risk.

 

Vos advises: "Because the lack of circulating statins is not the cause of atherosclerosis and their benefit on mortality is highly questionable, we should concentrate on lifestyle changes. Exercise, no smoking, and a healthy diet are well demonstrated in population studies to reduce the high mortality seen in so many economically developed countries".

 

He concludes that statins: "do not prevent cardiovascular and all-cause deaths".

 



Statin use associated with a 101% increased risk of diabetes

This study was published in Atherosclerosis 2015 Jul 15;242(1):211-217

 

Study title and authors:

Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis.

Shah RV, Allison MA, Lima JA, Bluemke DA, Abbasi SA, Ouyang P, Jerosch-Herold M, Ding J, Budoff MJ, Murthy VL.

Department of Cardiology and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/26209814

This study investigated the influence of statins and liver fat on type 2 diabetes. The study included 3,153 individuals who initially did not take statins and were without cardiovascular disease, or type 2 diabetes.

Regarding statins, the study found that individuals who took statins had a 101% increased risk of developing diabetes compared with individuals who did not take statins.

Statin use is associated with weight gain and a large increase in diabetes

This study was published in the Journal of the American Medical Association International Medicine 2014 Apr 24

 

Study title and authors:

Different Time Trends of Caloric and Fat Intake Between Statin Users and Nonusers Among US Adults: Gluttony in the Time of Statins?

Sugiyama T, Tsugawa Y, Tseng CH, Kobayashi Y, Shapiro MF.

Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California, Los Angeles2Department of Public Health/Health Policy, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan3Depa.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24763487

This study examined the effects of statins on caloric intake, weight gain and diabetes. The study lasted eleven years and included 27,886 adults, 20 years or older, who completed a 24-hour dietary recall.

The study found over an 11 year period:

(a) The caloric intake of statin users increased by 9.6%.

(b) The caloric intake of non users DECREASED by 1.9%.

(c) The BMI of statin user increased by 1.3

(d) The BMI of non users increased by 0.5

(e) Diabetes increased by 7.8% in statin users.

(f) Diabetes DECREASED by 0.4% in non users.

This study shows statin use is associated with weight gain and a large increase in diabetes.

 



Statin use associated with 87% increased risk of diabetes

This study was published in the Journal of General Internal Medicine 2015 Apr 28

Study title and authors:
Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults.

Mansi I, Frei CR, Wang CP, Mortensen EM
Department of Medicine, VA North Texas Health System, 4500 S. Lancaster Rd #111E, Dallas, TX, USA, Ishak.mansi@va.gov.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25917657

The objective of the study was to examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in healthy adults. The study lasted 8.5 years and included 3,351 statins users who were matched with 3,351 nonusers.

The study found:
(a) Statin users had a 87% increased risk of developing new-onset diabetes compared to nonusers.
(b) Statin users had a 150% increased risk of developing diabetes with complications compared to nonusers.
(c) Statin users were 14% more likely to be overweight or obese compared to nonusers.

Mansi concluded: "Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use".

Statins increase the risk of diabetes by 46%

This study was published in Diabetologia DOI 10.1007/s00125-015-3528-5

Study title and authors:
Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort
Henna Cederberg & Alena Stančáková & Nagendra Yaluri & Shalem Modi & Johanna Kuusisto & Markku Laakso
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital

This study can be accessed at: http://www.medscape.com/viewarticle/840884

The aim of this work was to investigate the mechanisms underlying the risk of type two diabetes associated with statins. The study included 8,749 non-diabetic men, aged 45–73 years, who were followed up for 5.9 years.

The study found:
(a) Individuals taking statins had a 46% increased risk of developing diabetes compared to individuals not taking statins.
(b)  Insulin sensitivity was decreased by 24% in individuals on statin treatment compared with individuals without statin treatment.
(c)  Insulin  secretion was decreased by 12% in individuals on statin treatment compared with individuals without statin treatment.

Cederberg concluded: "Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion".



Statin use is associated with an increased risk of type two diabetes, which increases with longer duration of use

This study was published in BMC Cardiovascular Disorders 2014 Jul 15;14(1):85

 

Study title and authors:

Statins and the risk of type 2 diabetes mellitus: cohort study using the UK clinical practice pesearch datalink.

Macedo AF, Douglas I, Smeeth L, Forbes H, Ebrahim S.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/25022519

This study aimed to assess the effect of statins on type two diabetes development. The study comprised of 2,016,094 individuals, including 430,890 people who received a statin, matched to 1,585,204 people not prescribed a statin.

The study found:
(a) Statin users had a 57% increased risk of developing diabetes compared to non-users.
(b) The risk of developing diabetes increased with longer duration of statin use:
(b1) Those who were followed for one to three years had a 22% increased risk of diabetes.
(b2) Those who were followed for 15 to 20 years had a 263% increased risk of diabetes.

Macedo concluded: "Statin use is associated with an increased risk of T2DM (type two diabetes), which increases with longer duration of use".

 



The risk of diabetes rises as adherence with statin therapy increases

This study was published in Diabetes Care 2014 Jun 26. pii: DC_132215

Study title and authors:
Statins and the Risk of Diabetes: Evidence From a Large Population-Based Cohort Study.

Corrao G, Ibrahim B, Nicotra F, Soranna D, Merlino L, Catapano AL, Tragni E, Casula M, Grassi G, Mancia G.
Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy giovanni.corrao@unimib.it.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24969582

The objective of the study was to investigate the relationship between adherence with statin therapy and the risk of developing diabetes. The seven year study included 115,709 patients who were newly treated with statins. Adherence was measured by the proportion of days covered with statins.

The study found: 
(a) Compared with patients with very-low adherence (proportion of days covered less then 25%) those with low adherence (proportion of days covered 26-50%) had a 12% increased risk of developing diabetes.
(b) Compared with patients with very-low adherence (proportion of days covered less then 25%) those with intermediate adherence (proportion of days covered 51-75%) had a 22% increased risk of developing diabetes.
(b) Compared with patients with very-low adherence (proportion of days covered less then 25%) those with high adherence (proportion of days covered more than 75%) had a 32% increased risk of developing diabetes.

Corrao concluded: "In a real-world setting, the risk of new-onset diabetes rises as adherence with statin therapy increases".

Possible mechanisms of how statins cause diabetes

This paper was published in Metabolism 2014 Feb 25

Study title and authors:
Statin treatment and new-onset diabetes: A review of proposed mechanisms.

Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS
Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24641882

Brault notes that new-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. Brault discusses the mechanisms that may be involved between statins and diabetes.

(a) Statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells.
(b) Statins reduce the expression of glucose transporter 4 (GLUT 4). GLUT 4 is a protein that transports glucose from the bloodstream into cells. Reduced GLUT 4 in response to statins results in hyperglycemia (high blood sugar) and hyperinsulinemia (excess levels of insulin in the blood).
(c) Statin therapy decreases other important molecules such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling.
(d) Statins interference with intracellular insulin signaling pathways via inhibition of necessary phosphorylation events (phosphorylation influences protein enzymes) and reduction of small GTPase action (GTPases are key proteins in many critical biological processes such as hormonal and sensory signals, and the protein building ribosomes). 
(e) Statins can decrease levels of peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which regulate glucose levels.
(f) Statins may also diminish levels of leptin and adiponectin which also play a role in regulating glucose levels.

Statins use is associated with increased HbA1c levels in patients with high blood pressure

This study was published in Diabetology and Metabolic Syndrome 2014 Apr 23;6:53

Study title and authors:
Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes.

Liew SM, Lee PY, Hanafi NS, Ng CJ, Wong SS, Chia YC, Lai PS, Zaidi NF, Khoo EM
Department of Primary Care Medicine, University of Malaya Primary Care Research Group (UMPCRG), Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24782916

This study sought to determine the association between the use of statins and glycaemic control in patients with high blood pressure. The study included 1,060 patients.

The study found:
(a) Analysis of the whole group found that statin users had 29% higher HbA1c levels than statin non users.
(b) Analysis of those with diabetes found that statin users had 20.8% higher HbA1c levels than statin non users.

Liew concluded: "Statins use is associated with increased HbA1c levels among hypertensive patients and hypertensive patients with diabetes".

Statins increase risk of diabetes by 32% in patients with impaired glucose tolerance

This study was published in the British Medical Journal 9 December 2013;347:f6745 

Study title and authors:
Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

Lan Shen

 

This study can be accessed at: http://www.bmj.com/content/347/bmj.f6745?rss=1

 

The objective of this study was to examine the association of various drugs in patients with impaired glucose tolerance with new onset diabetes. The study lasted five years and included 9,306 patients. (If you have impaired glucose tolerance, your blood glucose is raised beyond the normal range but it is not so high that you have diabetes. However, if you have impaired glucose tolerance you are at risk of developing diabetes).

 

Regarding statins, the study found that statin use was associated with a 32% increased risk of new onset diabetes.

Statins increase the risk of diabetes in kidney transplant patients

This study was published in Transplantation 2013 Nov 26

 

Study title and authors:

HMG CoA Reductase Inhibitor Treatment Induces Dysglycemia in Renal Allograft Recipients.

Choe EY, Wang HJ, Kwon O, Cho Y, Huh KH, Kim MS, Kim YS, Ahn CW, Cha BS, Lee HC, Kang ES.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/24285338

The aim of this study was to evaluate the influence of statins on the development of dysglycemia in kidney transplant patients. (Dysglycemia is defined as diabetes and impaired fasting glucose). The study included 394 patients without previously known diabetes or impaired fasting glucose who had undertaken kidney transplantation. Patients were grouped into the two groups according if they used statins (245 statin users and 149 nonusers).

The study found:
(a) Statin users had a 208% increased risk of dysglycemia compared to non users.
(b) The time to development of dysglycemia after transplantation was shorter in the statin group (38.8 months) than in the control group (47.2 months).

Choe concluded: "Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients (kidney transplant patients)".

Statin treatment increases cardiovascular diseases in diabetics by 31%

This study was published in Diabetes 2009 Apr;58(4):926-33

Study title and authors:

C-reactive protein and 5-year survival in type 2 diabetes: the Casale Monferrato Study.

Bruno G, Fornengo P, Novelli G, Panero F, Perotto M, Segre O, Zucco C, Deambrogio P, Bargero G, Perin PC.

Department of Internal Medicine, University of Torino, Torino, Italy. graziella.bruno@unito.it

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19074985

The objective of the study was to determine to what extent various diabetic risk factors and diabetic treatments influence 5-year cardiovascular death rates and total death rates in type 2 diabetic individuals. The study lasted for 5 years, with 11,717 years of observation on 2,381 subjects with type 2 diabetes.

The study found after 5 years:

• Those with C-reactive protein levels above 3 mg/l had an increase of 51% in total death rates and an increase of 44% in death from cardiovascular diseases compared to those with C-reactive protein levels below 3 mg/l. High fat diets can reduce dangerous C-reactive protein levels see here.
• Those with high blood sugar levels (HbA1-C) had an increase of 10% in total death rates and an increase of 19% in death from cardiovascular diseases compared to those with lower blood sugar levels. High fat diets can reduce dangerous high blood sugar levels see here.
• Those with LOW levels of high density lipoprotein (HDL) cholesterol had an increase of 8% in total death rates and an increase of of 1% in death from cardiovascular diseases compared to those with higher levels of HDL cholesterol. High fat diets raise the levels of the good HDL cholesterol see here.
• Those who were been treated with anti-diabetic drugs had an increase of 9% in total death rates and an increase of 24% in death from cardiovascular diseases compared to those who were not treated with anti-diabetic drugs.
• Those who were receiving insulin treatment had an increase of 81% in total death rates and an increase of 129% in death from cardiovascular diseases compared to those who were not receiving insulin treatment.
• Those who were taking statins had an increase of 2% in total death rates and an increases of 31% in death from cardiovascular diseases.

This study reveals many health risk factors linked with diabetes and higher death rates including high levels of C-reactive protein and blood sugar, and treatment with anti-diabetic drugs and statins.

Statins increase the risk of diabetes by 48%

This study was published in the Archives of Internal Medicine 2012 Jan 10

Study title and authors:

Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative.

Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, Manson JE

Department of Medicine, University of Massachusetts Medical School, Worcester;

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/22231607

This study investigated whether the incidence of diabetes is associated with statin use among postmenopausal women. The trial included 161,808 postmenopausal women aged 50 to 79 who were followed for 3 years which amounted to 1,004,466 person years of follow up.

The study found that statin use was associated with a 48% increase in diabetes.