The Importance of PPG Control

with Jaime A. Davidson, MD, FACP, MACE

Clinical Professor of Medicine, Touchstone Diabetes Center, University of Texas, Southwestern Medical Center, Dallas, TX


You may see patients in your practice with type 2 diabetes on a basal insulin who aren’t achieving target A1C goals, even though their fasting plasma glucose (FPG) levels are on track. While FPG is an important factor in managing the disease, the triad—FPG, postprandial glucose (PPG), and A1C—are all major factors in type 2 diabetes management.1 In fact, the first detectable glucose abnormality in patients with type 2 diabetes is PPG.2 Despite being a significant contributor to the overall glycemic load, PPG is often overlooked in favor of FPG.1 However, addressing a patient’s PPG levels may provide a clinically relevant guide to getting that patient to goal.1




I often discuss PPG and A1C control with colleagues. Here are some answers to the common questions I hear about the topic.

How should I address PPG in a patient with type 2 diabetes on basal insulin who is not achieving A1C goals?

In my practice, the first thing I do with a patient is check his or her glucose right there in the office. Ideally, that will help highlight the importance of PPG early. To demonstrate how uncontrolled PPG can affect your patients with type 2 diabetes who are not at A1C goal,1 let’s take a look at a profile of a patient type you may see in your practice. 

Patient profile: Jane

Jane presents with type 2 diabetes. She was diagnosed several years ago. Her FPG is controlled, but her A1C is uncontrolled at 7.9%, and her PPG is also uncontrolled. In order to reach her A1C goal, her treatment needs to be adjusted to focus on her PPG levels, as well. 

Patient Profile: Jane was diagnosed with type 2 diabetes. Her FPG is controlled, but her A1C is uncontrolled at 8%, and her PPG is also uncontrolled.

Headline


 

This case study examines a hypothetical patient profile. 


If Jane's FPG is controlled, why is her A1C still uncontrolled?

As you can see, there’s a missing piece in the considerations for Jane's treatment: PPG. I’ve found that my patients check their FPG, but they don’t understand the impact that PPG may have on their A1C goal. While FPG contributes to A1C, PPG is also an important part of A1C control.1 For some, uncontrolled PPG may actually lead to an increase in A1C levels.1


What’s the relationship between Jane's A1C and PPG?

The importance of PPG can change according to A1C control, as seen in the Monnier 2003 study of 290 patients with type 2 diabetes.3 After an overnight fast and standardized meals, the study found that in patients with poor control of their A1C (>10.2%), PPG contributes to roughly 30% of the 24-hour A1C.1 And in better controlled patients (A1C ≤7.3%), PPG accounts for roughly 70% of overall glycemic load.1

For Jane, this could mean that uncontrolled PPG may be contributing to her poorly controlled A1C. According to the Monnier 2003 study, as she gets closer to A1C goal, her poorly controlled PPG may only contribute more to the glycemic load.3



What therapy would you consider adding to help a patient like Jane get her PPG under control?


For some patients, a rapid-acting insulin analog may be more effective than basal insulin alone at helping them achieve blood glucose control.1 Patients in the Treating to Target Type 2 Diabetes trial (4-T trial), were intensified with NovoLog® in a basal-bolus regimen, and as a result a majority attained and maintained A1C ≤7% within the 3-year study.4,5

For a patient like Jane, I would consider adding a mealtime insulin like NovoLog® to her treatment regimen. The FullSTEP® stepwise approach—a manageable, patient-titrated method for glycemic control—may be an option to help Jane initiate NovoLog®.  



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PPG contributes a significant amount to overall glycemia. Adding mealtime insulin like NovoLog® might help to reach an A1C goal.


 

When you see patients like Jane who have uncontrolled A1C and controlled FPG, take a look at the patient’s PPG levels. This might be the missing piece that is keeping the patient from achieving his or her A1C goal.1 Regardless of whether you’re treating a patient who has well-controlled A1C levels or not, keep in mind that PPG still contributes a significant amount to the overall glycemia.Beyond adding mealtime insulin, you may need to make more adjustments. In this case, I would also remove the glipizide, because it is no longer needed to reach Jane's goal. 


What tools are available for addressing PPG?

For me, one of the most important parts of starting patients on insulin is the support they get. In my practice, we use a number of the resources that Novo Nordisk offers. For example, CheckPoints is a Novo Nordisk program designed to help patients transition to mealtime insulin, and offers resources to help them learn more about PPG and rapid-acting insulin analogs. This includes a teaching tool to help educate your patients on their disease, posters for your practice, and the Testing in Twos PPG tracker. With the Testing in Twos tracker, patients can test and record their PPG before and after their largest meal, allowing them to see how meal choices can impact PPG. Cornerstones4Care® has even more tools and resources your patients can tailor to their needs, wherever they are in their diabetes journey.


 



Monnier 2003 study design
In 290 non-insulin and non-acarbose-using patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 am) and during postprandial and postabsorptive periods (at 11:00 am, 2:00 pm, and 5:00 pm). The areas under the curve above fasting PG concentrations (AUC1) and >6.1 mmol/l (AUC2) were calculated for further evaluation of the relative contributions of postprandial (AUC1/AUC2, %) and fasting [(AUC2-AUC1)/AUC2, %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of A1C.3

4-T trial study design
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 were 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®. The results of this arm of the study are shown here. 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®.4,5

FullSTEP® study design
Rodbard et al (FullSTEP®), a randomized, open-label, multinational, non-inferiority, 32-week, treat-to-target trial. Patients with type 2 diabetes inadequately controlled on basal insulin with or without oral antidiabetic drugs were randomized to either a stepwise arm or full basal-bolus arm. In the stepwise arm (n=201), NovoLog® was initially added to basal insulin at the patient-perceived largest meal. Additional doses were added to the next largest patient-perceived meal at weeks 11 and 22 if A1C ≥7%. In the full basal-bolus arm (n=200), NovoLog® was added at all 3 main meals from the start. Patients in both arms self-titrated NovoLog® daily based on the previous day’s pre-meal or bedtime SMPG levels.7    

 

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. Leiter L, Ceriello A, Davidson J, et al. Postprandial glucose regulation: new data and new implications. ClinTher. 2005;27:S42-S56. 
  2. Guideline for management of postmeal glucose in diabetes 2011. International Diabetes Foundation website. http://www.idf.org/2011-guideline-management-postmeal-glucose-diabetes. Accessed January 27, 2016.
  3. Monnier, L., Lapinski, H., & Colette, C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care. 2003;26(3):881-885.
  4. Holman RR, Farmer AJ, Davies MJ, et al; for the 4-T Study Group. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.
  5. Holman RR, Thorne KI, Farmer AJ, et al; for the 4-T Study Group. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716-1730.
  6. Parkin C, Brooks N. Is postprandial glucose control important? Is it practical in primary care settings? Clin Diabetes. 2002;20(2):71-76. 
  7. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DHW. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol. 2014;2:30-37.