The Impact of Overbasalization

with James R. LaSalle, DO, FAAFP

Excelsior Springs Clinic, Excelsior Springs, MO


Over the last several years, the number of diabetes caseloads has grown, and the trend will likely continue.1 As you know, basal insulin is a widely accepted treatment for managing type 2 diabetes. But, the progressive nature of diabetes means that eventually some of your patients may need to add more treatments.2 For your patients who aren’t achieving their blood sugar and A1C goals, staying on basal insulin alone may put them at risk for overbasalization.3 Understanding how to spot overbasalization and identifying patients who need to add mealtime insulin may help these patients get their A1C under control.




I often discuss the impact of overbasalization with my colleagues. Here are some answers to the common questions I hear about the topic.

What is overbasalization?

When patients on basal insulin no longer see the effects of treatment even with larger doses, then they are experiencing overbasalization.3 Part of the reason for overbasalization is due to the lack of upper limits for basal titration.3 With no well-defined limits, you may consider increasing your patients’ basal insulin doses to help achieve A1C goals. However, if they are experiencing overbasalization, adding more basal insulin may not give them the blood glucose and A1C control they need. For some patients, increasing basal insulin only provides additional glycemic control up to a certain point beyond a standard dose, and that limit may not be the same for each patient.3 This can lead to confusion about the next steps in treatment. 

Due to the natural progression of diabetes, you will likely have to make some changes to your patients’ treatment regimens over time.2 Preventing overbasalization is ideal, but it doesn't always happen. Understanding the impact and how to alter treatment may help your patients reach their treatment goals.3  

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What's the impact of overbasalization?

When basal insulin doses are increased to the point at which additional glycemic control is no longer provided, patients spend a longer amount of time in an uncontrolled state. In general, this can make glycemic control difficult to achieve,4 which can make it even harder for your patients to manage their disease.

Also, overbasalization may change the pharmacokinetics of basal insulin. For some, the profile of the basal insulin changes from no pronounced peak to a profile with an insulin peak.3 If the profile changes, this may lead to an increased risk for adverse events like hypoglycemia.3




Why is basal insulin no longer effective at certain doses?

Basal insulin can lower FPG, which can help patients with type 2 diabetes achieve their blood sugar target and A1C goals; however, postprandial glucose (PPG) also impacts A1C and should also be a factor when monitoring your patients during the disease management. Even when FPG is at target, an increase in PPG control can contribute to overall glycemic control (A1C).

While increasing basal insulin doses might seem like the path to achieving A1C goals, the patient may be at risk for overbasalization.3 In fact, in the Treating to Target Type 2 Diabetes trial (4-T trial), 82% of patients in the basal arm needed to add mealtime insulin by the end of year 1 to reach A1C goals.5

See the 4-T trial study design below.



How do I know if a patient may need to add mealtime insulin?

Mealtime insulin may be an option for your patients that are uncontrolled on basal insulin.3 Here are some guidelines to help assess if a patient may need to add a mealtime insulin to their basal treatment:


Calendar: FPG at target but A1C target <7% not reached after 3 to 6 months; Arrow in the middle of board: PPG in not at goal but FPG may be at goal; Weighing scale: Basal insulin dose exceeding 0.5 units/kg of body weight



In my practice, I prefer to evaluate treatment at 3 months and make changes if a patient is not at goal.6 From my view, early control of A1C may help reduce the risk of diabetes-related complications.

aAmerican Diabetes Association recommendations for PPG and FPG in patients with type 2 diabetes.


Can mealtime insulin help address overbasalization in my patients?

NovoLog® is a rapid-acting insulin analog that is engineered for mealtime use, by closely mimicking the body's normal mealtime insulin response.3 NovoLog® is a safe, effective and rapid acting insulin proven to help control blood sugar spikes after meals.8

When a patient has reached the point where uptitration of basal insulin is no longer effective in achieving A1C goals, it’s likely that you need to reassess his or her treatment and make adjustments. For example, adding a rapid-acting insulin analog, like NovoLog®, may be an appropriate addition to that patient’s basal treatment regimen.3



How do I start my patient on NovoLog®?

Novo Nordisk has a number of tools available to facilitate the process of starting your patients on NovoLog®. First, the FullSTEP® study stepwise approach—a manageable, patient-titrated method for glycemic control—may help your patients initiate and maintain mealtime insulin. You can also help your patients learn more about mealtime insulin with CheckPoints, a teaching tool that your practice can use to help educate your patients on the progression of their disease, track PPG, and more. Support your patients as they initiate/add mealtime insulin to their treatment plan, and teach them about rapid-acting insulin analogs with CheckPoints.







4-T trial study design
Holman et al (4-T trial), a 3-year, multicenter, randomized, treat-to-target study of 708 insulin-naïve patients with type 2 diabetes. A total of 234 patients were randomized to insulin detemir and intensified with NovoLog® if A1C was >10% after 1 measurement or ≥8% for 2 consecutive measurements at or after 24 weeks, or if A1C was >6.5% at 1 year. At study end, 82% of patients had been intensified with NovoLog®. In addition, 239 patients were randomized to NovoLog® and 235 patients were randomized to biphasic insulin aspart 30 (results not shown). All insulin was delivered by FlexPen®.5

Selected Important Safety Information

Contraindications

  • NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients. 

Warnings and Precautions

  • Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 
  • Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously under close medical supervision and the frequency of blood glucose monitoring should be increased.

NovoLog® (insulin aspart injection) 100 U/mL Indications and Usage

NovoLog® (insulin aspart injection) 100 U/mL is an insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus. 

Important Safety Information

Contraindications

  • NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients. 

Warnings and Precautions

  • Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 
  • Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made cautiously under close medical supervision and the frequency of blood glucose monitoring should be increased. 
  • Hypoglycemia is the most common adverse effect of insulin therapy. The timing of hypoglycemia may reflect the time-action profile of the insulin formulation. Glucose monitoring is recommended for all patients with diabetes and is particularly important for patients using external pump infusion therapy. 
  • To avoid medication errors and accidental mix-ups between NovoLog® and other insulin products, instruct patients to always check the insulin label before injection. 
  • Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog®
  • As with all insulins, NovoLog® use can lead to life-threatening hypokalemia, which then may cause respiratory paralysis, ventricular arrhythmia, and death.  Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
  • Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered. 
  • Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure. 

NovoLog® continuous subcutaneous infusion route (insulin pump): Do not mix NovoLog® with any other insulin or diluent. 

Adverse Reactions

  • Adverse reactions observed with NovoLog® include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus. 

Use in Specific Populations

  • NovoLog® has not been studied in children with type 2 diabetes or in children with type 1 diabetes who are younger than 2 years of age. 
  • Like all insulins, NovoLog® requirements may be reduced in patients with renal impairment or hepatic impairment. These patients may require more frequent blood glucose monitoring and dose adjustments. 

Please click here for Prescribing Information.

 

References:

  1. National diabetes statistics report, 2017. Centers for Disease Control and Prevention website. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed May 21, 2018.
  2. Raccah D, Bretzel R, Owens D, Riddle M. When basal insulin therapy in type 2 diabetes mellitus is not enough—what next?. Diabetes Metab Res Rev. 2007;23(4):257-264.
  3. LaSalle JR, Berria R. Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. Berria R, ed. J Am Osteopath Assoc. 2013;113(2):152-162.
  4. Garber HJ. Insulin intensification strategies in type 2 diabetes; when one injection is no longer sufficient. Diabetes Obes Metab. 2009;11(suppl 5):14-18. 
  5. Holman RR, Farmer AJ, Davies MJ, et al; 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361:1736-1747.
  6. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Updated position statement of the American Diabetes Association and the European Association for the Study of Diabetes, Diabetes Care. 2015;38:140-149.
  7. Unger J, Schwartz Z. Diabetes Management in Primary Care. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.
  8. Lindholm A, McEwen J, Riis AP. Improved postprandial glycemic control with insulin aspart: a randomized double-blind cross-over trial in type 1 diabetes. Diabetes Care. 1999;22(5):801-805.