Wednesday, February 15, 2012

Diabetes medication , the first choice is easy, the second choice is not as easy

Save time just read the yellow highlighted areas also you may want to review the last few days discussion about GPL-1 Agonist and DPP-4 inhibitors before reading this.

Two articles caught my eye this morning and resulted in my reviewing the medication recommendations for the treatment of type 2 diabetes. I reviewed the American Diabetes Association , American college of Physicians . I believe there is general agreement that metformin(glucophage) is the first medication  
to use.

Most people will need a second medication  at some point in their diabetes care. The choice of  a second medication involves more variables such as COST , weight gain or loss , age , heart , brain and kidney status, risk of hypoglycemia , lack of long term risk/ benefit data and others.

The choice of the second medication is a clinical decision  made by you and your physician based on the best information available  at that moment

Guide lines

Ann Intern Med. 2012 Feb 7;156(3):218-231.
Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians.
the American College of Physicians, Philadelphia, Pennsylvania; Oregon Health & Science University, Portland, Oregon; University of Kansas School of Medicine, Wichita, Kansas; and West Los Angeles Veterans Affairs Medical Center, Los Angeles, California.
Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications. Methods: This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. 
Recommendation 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). 
Recommendation 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence).
 Recommendation 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).Ann Intern Med. 2011 May 3;154(9):602-13. Epub 

American Diabetes Association Standards of care 2011

2011 Mar 14. 2. Therapy for type 2 diabetes
The ADA and the EASD published an expert
consensus statement on the approach
to management of hyperglycemia in individuals
with type 2 diabetes (82). Highlights
of this approach are: intervention at
the time of diagnosis with metformin in
combination with lifestyle changes (MNT
and exercise) and continuing timely augmentation
of therapy with additional
agents (including early initiation of insulin
therapy) as a means of achieving and
maintaining recommended levels of glycemic
control (i.e., A1C 7% for most

Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations.

The Johns Hopkins University School of Medicine and The Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Baltimore, MD 21205, USA.
Erratum in
Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices.
To summarize the benefits and harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes.
Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms.
Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality.
Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A(1c) level by about 1 percentage point and most 2-drug combinations produced similar reductions. 
Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about -2.5 kg. 
*Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. 
Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. 
Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones.
Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits.
Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A(1c) levels, but some increased risk for hypoglycemia and other adverse events. Primary Funding Source: Agency for Healthcare Research and Quality.

*comment . I recall an article that found a decrease in LDL and Triglycerides and an increase in HDL cholesterol when using  GLP1 agonist  as their second drug.

Have Fun, be Smart and Defeat Diabetes
David Calder,MD

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Your comments and questions are appreciated. David Calder,MD