Expert Blog

A Primary Care View On Case 3: Two Orals Fail

Doron Schneider, MD, FACP
General Internist

Our patient represents a common scenario in primary care–failure to get to goal A1C despite taking two oral diabetic medications. The most critical point I can make is to do something! Diabetes is a progressive disease, and without a significant weight loss our patient’s A1C will continue to climb. This patient, like many, has found it difficult to maintain weight loss for a prolonged period of time. While one could consider more extreme interventions that may promote weight loss—such as medically supervised low-calorie diet plans or even certain types of bariatric surgery—most patients are unwilling to consider these alternatives. Thus, intensification of medications becomes the most immediate and efficacious therapeutic option.  

As we ponder medication options, I would also point out several general observations regarding this patient’s overall care:
  • This patient has been seen every six months. During this next intensification of therapy phase, I would consider increasing the frequency of contact. Office visits that occur at three month intervals are reasonable until she gets to goal. Between visits phone calls can also be used to review blood sugar data to make additional medication adjustments.
  • To enhance overall medication adherence, I would combine the lisinopril and hydrochlorthiazide into one tablet. I would do the same with the metformin and glipizide and prescribe metaglip (she has insurance coverage, and this should be covered). Decreasing her overall pill burden will maximize adherence.
  •  I would look critically at her use of aspirin and determine if the risk-benefit ratio favors continuation (if her risk of cardiac event in the next ten years was less than 10%, I would stop this drug).
  • Given her elevated BMI I would screen her for sleep apnea. Patients with type 2 diabetes have very high risk of having sleep apnea, and initiating CPAP on such patients has been shown to improve multiple cardiometabolic endpoints.
Now that I have gotten all that off my chest, let’s ponder the selection of the next medication.  I take this opportunity to echo the key points made by our case discussants and add additional points.
Any therapeutic decision needs to be tailored to the needs of the individual patient. Our patient has several key points that are relevant to consider when deciding on the TZD option:
  • Age.  This patient’s age places her at potential increased fracture risk. As noted by our discussant, TZDs are also associated with an increased fracture risk. Prior to prescribing a TZD a bone density test may be warranted. Additionally, attention to dietary calcium intake, measuring vitamin D levels, and as-needed supplementation of each are good primary care basics. If the decision to use a TZD is made, a reasonable approach would be to use a middle-of-the-road dose to mitigate any fracture risk and provide good metabolic effects.
  • Cardiac risk factors.  The literature and understanding of the cardiac impact of TZDs is rapidly evolving. The need to stay attuned to this literature is paramount, and the clinician is challenged to develop mechanisms to remain engaged in perpetual self-education (subscribing to this site is one way!)
  • Weight.  TZDs can certainly lead to weight gain. Preparing the patient for this is essential. Having the patient set reasonable self-directed goals can encourage increased exercise and decrease caloric intake. Additionally, edema formation can be mitigated with direction to minimize salt intake. Counseling to avoid foods with high salt levels such as canned soups, deli meats, and rice mixes is a start. Patients are often simply unaware of these basics.
  •  Other diabetes medications.  Adding a TZD can increase the risk of hypoglycemia when added to a sulfonylurea. The patient should be told to increase her blood sugar monitoring. A dose reduction of her sulfonylurea may be necessary
GLP-1 Agonists
Looking at our patient once again we view some of her defining characteristics in the context of the  GLP-1 agonist option:
  • Age.  There are no significant age-related barriers to prescribing a GLP -1 agonist .
  • Weight.  GLP-1 agonists slow stomach emptying, increase sense of fullness, and cause early satiety. These properties may explain the weight loss associated with these agents, rather than the nausea, which, whilecommon early in the course of therapy, may be minimized by slow up-titration of the dose
  • Cardiac risk factors.  GLP-1 agonists are associated with reduced blood pressure, improved lipid profile, and increased vasodilatory activity.  However, it is simply unknown if these agents can actually reduce the risk of cardiovascular endpoints of interest (e.g., myocardial infarction, congestive heart failure, and cerebrovascular accidents)
  • Other agents.  GLP-1 agonists can be added to metformin and sulfonylureas. As with TZDs, however, because combination may increase hypoglycemia risk , the sulfonylurea dose should be decreased during the intensification phase of the GLP-1 agonist.
Unlike the TZD option, GLP agonists (like insulin) have an associated “injection barrier.”  This can be overcome by:
  1. Discussing the relatively painless injection afforded by the currently available fine needles. 
  2. Administering the first injection in the office.
  3. Establishing a system in the office that offloads the entire responsibility for teaching away from the doctor (e.g., having a nurse or medical assistant trained to provide the education and teaching to patients).
Due to progressive beta cell failure many diabetic patients will eventually require insulin. While an extremely potent option for glucose reduction, insulin is limited in efficacy by its real and theoretical potential to cause hypoglycemia. This risk may explain the lack of intensification frequently seen in primary care. Physicians and patients alike thus need to have the knowledge and skills to use insulin optimally.  Developing comfort with algorithms to initiate and intensify insulin will help practices get more patients to goal. As with GLP-1 agents, practices need to establish systems to overcome the injection and teaching barrier. Sitting down with the office manager, staff, and other partners to discuss this problem will lead to workable local solutions.
With this background, let’s review our patient’s defining characteristics in light of the insulin option:
  • Age.  There are no significant age-related barriers to prescribing insulin. More elderly patients may be at greater risk of adverse outcomes from hypoglycemia,  at 67 our patient presents no special considerations for insulin.
  • Weight.  Patients who are initiated on insulin gain weight, a problem with which our patient has struggled for years. Patients need to be told about weight gain when initiating insulin in order to develop strategies to mitigate it. Encouraging a visit to a dietician may help patients understand sources of “empty calories” that can be removed from the diet, provide skills for calorie counting, etc. Weight Watchers is an excellent program to recommend at the same time insulin initiation. Bundling this approach (insulin and weight management considerations) is advised.
  • Cardiac risk factors.  Recent studies have associated very low glycemic targets with a higher mortality, possibly attributable to higher rates of hypoglycemia with resultant stress on the cardiovascular system.  Providers can mitigate this risk when prescribing insulin to patients with cardiac disease or multiple risk factors for cardiac disease by paying careful attention to hypoglycemia. Patients need to be taught the signs of hypoglycemia, the need to monitor their sugars and log them (both regularly and when they sense they may becoming hypoglycemic). Patients need to be taught when to contact the office due to hypoglycemia as opposed to waiting for their next appointment. Patients practicing self-titration need to demonstrate clear understanding of how to change doses when hypoglycemia occurs 
  • Other agents.  Our patient is on a sulfonylurea and metformin. Due to the increased risk of hypoglycemia it is appropriate to stop a long-acting sulfonylurea when initiating basal insulin.
As outlined above, there are no perfect solutions or approaches to our patient. Each option has benefits, risks and costs. The most salient point to make is to DO SOMETHING! Often the most difficult thing to overcome is the inertia that keeps us from making change.