On 2017 Oct 28, Daniel Weiss commented:

Karter et. al describe a tool to predict the risk of hypoglycemia in persons with Type 2 Diabetes. This tool confirms obvious, well-established clinical observations: sulfonylureas and insulin are associated with an increased risk of hypoglycemia. Three points are worth clarifying.

First, this tool was developed in the Kaiser Permanente of Northern California health care system where practitioners have a very limited choice of agents for Type 2 Diabetes. In that system and the Veterans Health Administration, the usage of drugs that do not tend to cause hypoglycemia is restricted due to cost. Yet, glucagon-like peptide-1 (GLP-1) receptor agonists have been available since 2005 and the first sodium-glucose cotransporter-2 (SGLT2) inhibitor was approved in 2013. Although less effective, dipeptidyl peptidase-4 (DPP-4) inhibitors have been around since 2007. All these drug classes cost more than sulfonylureas but none put patients at risk for hypoglycemia.

In large part, because of that risk of hypoglycemia, the American Association of Clinical Endocrinologists algorithm (1) for pharmacotherapy of Type 2 Diabetes judges sulfonylureas as the worst option. Indeed, the annual rate of hypoglycemia was lowest in the Group Health Cooperative patients where sulfonylureas were used less frequently.

Second, the authors fail to account for the type of insulin prescribed. They lump all insulins together. And they discuss skipping meals as a cause of hypoglycemia. All insulins are not the same. For example, NPH insulin is associated with a greater risk of hypoglycemia than is insulin glargine in head to head trials (2). And the pharmacokinetics of NPH insulin are such that insulin levels often peak when the patient is not eating. Well-designed insulin regimens allow patients to skip meals with no problem.

Third, in their lengthy discussion on steps to reduce the risk of hypoglycemia, the authors fail to even mention choosing effective agents that do not cause hypoglycemia such as GLP-1 receptor agonists or SGLT-2 inhibitors. And some of these newer agents have now been demonstrated to reduce cardiovascular events and mortality.

The authors focus on population approaches, not the best care for the individual patient in the exam room.

Conflict of Interest Disclosures: This commenter receives clinical research funding and speaker honoraria from multiple pharmaceutical companies that market medication for diabetes.

1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm - 2017 Executive Summary. Endocr Pract. 2017;23(2):207-238.
2. Riddle MC, Rosenstock J, Gerich J, Insulin Glargine Study I. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080-3086.

On 2017 Oct 28, Daniel Weiss commented:

Karter et. al describe a tool to predict the risk of hypoglycemia in persons with Type 2 Diabetes. This tool confirms obvious, well-established clinical observations: sulfonylureas and insulin are associated with an increased risk of hypoglycemia. Three points are worth clarifying.

First, this tool was developed in the Kaiser Permanente of Northern California health care system where practitioners have a very limited choice of agents for Type 2 Diabetes. In that system and the Veterans Health Administration, the usage of drugs that do not tend to cause hypoglycemia is restricted due to cost. Yet, glucagon-like peptide-1 (GLP-1) receptor agonists have been available since 2005 and the first sodium-glucose cotransporter-2 (SGLT2) inhibitor was approved in 2013. Although less effective, dipeptidyl peptidase-4 (DPP-4) inhibitors have been around since 2007. All these drug classes cost more than sulfonylureas but none put patients at risk for hypoglycemia.

In large part, because of that risk of hypoglycemia, the American Association of Clinical Endocrinologists algorithm (1) for pharmacotherapy of Type 2 Diabetes judges sulfonylureas as the worst option. Indeed, the annual rate of hypoglycemia was lowest in the Group Health Cooperative patients where sulfonylureas were used less frequently.

Second, the authors fail to account for the type of insulin prescribed. They lump all insulins together. And they discuss skipping meals as a cause of hypoglycemia. All insulins are not the same. For example, NPH insulin is associated with a greater risk of hypoglycemia than is insulin glargine in head to head trials (2). And the pharmacokinetics of NPH insulin are such that insulin levels often peak when the patient is not eating. Well-designed insulin regimens allow patients to skip meals with no problem.

Third, in their lengthy discussion on steps to reduce the risk of hypoglycemia, the authors fail to even mention choosing effective agents that do not cause hypoglycemia such as GLP-1 receptor agonists or SGLT-2 inhibitors. And some of these newer agents have now been demonstrated to reduce cardiovascular events and mortality.

The authors focus on population approaches, not the best care for the individual patient in the exam room.

Conflict of Interest Disclosures: This commenter receives clinical research funding and speaker honoraria from multiple pharmaceutical companies that market medication for diabetes.

1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm - 2017 Executive Summary. Endocr Pract. 2017;23(2):207-238.
2. Riddle MC, Rosenstock J, Gerich J, Insulin Glargine Study I. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080-3086.