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In the Clinic |

Type 2 Diabetes

Sandeep Vijan
[+] Article, Author, and Disclosure Information

CME Objective: To review current evidence for prevention, screening, diagnosis, treatment, and patient information of type 2 diabetes.

Funding source: American College of Physicians.

Disclosures: Dr. Vijan, ACP Contributing Author, has disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2388.

With the assistance of additional physician writers, Annals of Internal Medicine editors develop In the Clinic using resources of the American College of Physicians, including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program).

Ann Intern Med. 2015;162(5):ITC1. doi:10.7326/AITC201503030
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This issue provides a clinical overview of Type 2 Diabetes focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.





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In The Clinic, Type 2 Diabetes
Posted on March 25, 2015
David S. H. Bell, MB
Southside Endocrinology
Conflict of Interest: Takeda Pharmaceuticals - Consultant and Speaker
Dr. Sandeep Vijan in his review of type 2 diabetes states that treatment with sulfonylureas and thiazolidinediones in particular cause hypoglycemia and weight gain.1

While both sulfonylureas and thiazolidinediones clearly cause weight gain only sulfonylureas and not thiazolidinediones cause hypoglycemia.

Thiazolidinediones cause weight gain not only through better glycemic control, less glycosuria and preservation of calories but also through fluid retention due to the presence in the very distal renal tubule of p-par-gamma receptors. As a result, loop or thiazide diuretics which act at more proximal tubular sites do not result in diuresis or a weight loss.2 However, utilization of diuretics such as eperolone, spironoloactone and amiloride which act on the distal tubule can result in a diuresis and weight loss.2

Clearly thiazolidinediones do not cause hypoglycemia when used as monotherapy or in combination with drugs such as metformin, α-glucosidase inhibitors. DPP-4 and SGLT2-inhibitors and incretin mimetics which when utilized as monotherapy do not cause hypoglycemia. Only, when thiazolidinediones are utilized with drugs that cause hypoglycemia - sulfonylureas, glynides and insulin, does hypoglycemia occur.3

To avoid hypoglycemia and its consequences drugs that do not cause hypoglycemia should be preferred in the therapy of type 2 diabetes.4

1) Sandeep, V. In the Clinic: Type 2 Diabetes. Annals Intern Med(2015)ITCI-14.
2) Chraïbi A, Renauld S. PPARγ-induced stimulation of amiloride-sensitive sodium current in renal collecting duct principal cells is serum and insulin dependent. Cell Physiol Biochem(2014)33(3):581-93.
3) Vlckova V, Cornelius V, Kasliwal R, Wilton L, Shakir SA. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide. Drug Saf(2009)32(5):409-18.
In response
Posted on June 9, 2015
Sandeep Vijan, MD
Ann Arbor VA Health System; University of Michigan Medical School
Conflict of Interest: None Declared
I agree with the letter from Dr. Bell. Thiazolidinediones do not cause hypoglycemia as monotherapy. This was misstated in the initial manuscript; the intent was to suggest that they can cause hypoglycemia in combination with other drugs (such as insulin or sulfonylureas). Weight gain is a clear side effect of thiazolidinediones, and as noted in the letter, is in large part due to fluid retention, and has been associated with higher rates of congestive heart failure.(1)

I also agree that avoidance of hypoglycemia is a very important consideration with choice of treatment agents. The choice of agent after metformin remains difficult, however, given the lack of clear long-term data on changes in clinical outcomes with many of the newer glucose lowering agents. Other considerations, particularly patient preferences, cost, and additional side effect profile, along with the expected magnitude of the benefits of intensifying glucose control in a given individual, should dictate the need for and choice of medication.

1. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet. 2007 Sep 29;370(9593):1129–36.

Avoidance of hypoglycemia and preservation of residual beta cell mass are the two vital targets during the management of hyperglycemia in type 2 diabetes
Posted on August 7, 2015
Gauranga Dhar
Bangladesh Institute of Family Medicine and Research
Conflict of Interest: None Declared
It is extremely important that to avoid hypoglycemia is one of the main goals of the management of hyperglycemia and I think another main goal should be the preservation of residual beta cells. So, selection of anti-hyperglycemic agent is a big challenge.
Now a days after number of studies when some countries have already banned pioglitazone, we cannot go for this drug as first line monotherapy and metformin remains first line anti-diabetic agent for type 2 diabetes patients. I am completely agree with Dr. Bell that after metformin we can go for other agents like DPP-4 inhibitors, GLP-1 agonists, alpha-glucosidase inhibitors, SGLT-2 inhibitors and even pioglitazone. These agents do not act on beta cells and combination of these drugs will not cause hypoglycemia and will help in the preservation of residual beta cells.
Although we are randomly using these drugs, still we do not have clear safety data (as mentioned by Dr. Sandeep) of any of the above agents. Still we do not know how safe pioglitazone in terms of bladder or pancreatic cancer is. Are incretin based drugs really safe in terms of pancreatitis and cardiovascular adverse effects? How safe are SGLT-2 inhibitors in terms of developing UTI, fungal infection and euglycemic ketoacidosis? In addition, cost of newly introduced of the above agents also a concern.
For proper management of hyperglycemia, diabetologists should agree that in majority of cases, combination of the above mentioned drugs is not enough and for this reason we need to go for insulin secretagogues, specifically sulfonylureas along with one or two of the above mentioned drugs but dose of the secretagogue should be selected in such way so that we can avoid hypoglycemia.
We should avoid hypoglycemia as well as we also need to preserve residual beta cell mass. In this case I think that the most authentic way to treat hyperglycemia is to start basal insulin if metformin monotherapy fails but adherence to injectable form is a problem.
We should follow the guideline but management options should be individualized.

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