#433 CGMs, Insulin, and How to Adjust Diabetes Meds to Glucose Patterns

April 1, 2024 | By Matthew Watto, MD

Audio

Video

Transcript available via YouTube

Step up your diabetes game! Learn the ins and outs of continuous glucose monitors (CGM) including key features, what and how to order, interpreting CGM data (time in range, time above range, etc.), and how to make adjustments to a patient’s insulin regimen, aka “insulin pattern matching”. We discuss common scenarios including overnight hypoglycemia, exercise-induced hypoglycemia, post-prandial hyperglycemia, what to do when the patient runs high all the time, and how to incorporate GLP1 agonists and SGLT2 inhibitors into a patient’s regimen. Returning guest and Paul’s favorite frenemy, Dr. Jeff Colburn (VCU Health) returns!

Claim CME for this episode at curbsiders.vcuhealth.org!

Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME

Show Segments

• 00:00 Introduction and Diabetes Puns
• 01:00 Introduction of Guest and Topic
• 09:12 Qualifications and Eligibility for CGMs
• 11:32 Types of CGMs and Sensor Placement
• 24:47 Interpreting CGM Data and Alarms
• 34:30 Troubleshooting Patterns and Adjustments
• 35:23 Understanding Hypoglycemia and Counter Regulatory Hormone Responses
• 36:15 The Rule of 15 and Addressing Hypoglycemia
• 37:10 Reducing Basal Insulin to Address Nocturnal Hypoglycemia
• 38:29 Addressing Postprandial Highs with GLP-1, SGLT-2 Inhibitors, or Prandial Insulin
• 39:51 Managing Exercise-Induced Hypoglycemia
• 41:43 Preventing Exercise-Induced Hypoglycemia with Snacks
• 43:42 Managing Nocturnal Hypoglycemia with Sulfonylureas
• 45:31 Addressing Postprandial Hyperglycemia with GLP-1, SGLT-2 Inhibitors, or Prandial Insulin
• 46:54 Adjusting Basal Insulin to Address Morning Hyperglycemia
• 51:18 Troubleshooting High Blood Sugars with Basal Insulin and Mealtime Insulin
• 56:49 Managing High Blood Sugars with Basal Insulin and Mealtime Insulin
• 57:44 Addressing Adherence and Medication Barriers
• 59:39 Using Continuous Glucose Monitors (CGMs) for Diabetes Management
• 01:02:30 Using Sulfonylureas and Basal Insulin Combination as a Stopgap
• 01:05:49 Considering Patient Adherence and Barriers to Treatment

CGMs and Pattern Matching Pearls

1. Since April 2023, CMS says any patient with 1) diabetes taking insulin at least once daily or 2) problematic hypoglycemia is eligible for a continuous glucose monitor (CGM).
2. Patients wearing a CGM commonly see reduced A1C values even without any changes to therapy (Vigersky, 2012; Jancev, 2024).
3. CGM sensors are worn for 10-14 days so order 2-3 sensors per month. Smartphones can act as the receiver to display values.
4. CGM metrics: Goal time-in-range 70-180 mg/dL = >70%, above-range >180 mg/dL <30%, and below range <5%. Graphs display glucose trends to identify when highs and lows occur.
5. Metformin and basal insulin mainly target fasting blood glucose. GLP1 agonists and SGLT2 inhibitors lower both fasting and post-prandial glucose.
6. Evaluating blood glucose patterns. Step 1: address any hypoglycemia. Step 2: target hyperglycemia addressing fasting glucose first followed by mealtime needs.
7. Nocturnal hypoglycemia fixes: Reduce the basal insulin dose. Omit the evening sulfonylurea dose if taken twice daily, and reduce or stop long-acting sulfonylurea agents. 
8. Exercise-induced hypoglycemia: Reduce the basal insulin dose or the preceding mealtime insulin, or take a snack with complex carbohydrates, protein, and fat (e.g. half a banana and peanut butter) prior to exercise.
9. Rapid-acting insulin should not be given between meals to avoid “stacking” doses.

A1C refresher

Recall that an average blood sugar of 126 mg/dL is equivalent to an A1C of 6% and the A1C increases by 1% for every ~30 mg/dL increase in blood glucose (i.e. 154 mg/dL = 7%, 183 mg/dL = 8% and so forth) —ADA eAG/A1C Conversion Calculator accessed 17 March 2024.

Continuous Glucose Monitors

Since April 2023, CMS says any patient with 1) diabetes taking insulin at least once daily or 2) problematic hypoglycemia is eligible for a continuous glucose monitor (CGM). A follow-up with the treating clinician every six months is required to “document adherence to their CGM regimen and diabetes treatment plan” (CMS.gov L33822 accessed 17 Mar 2024).

Studies suggest that patients wearing a CGM see an improvement in A1C values even without any changes in therapy (Vigersky, 2012; Jancev, 2024). Dr. Colburn hypothesizes this occurs due to immediate feedback on eating behaviors. 

CGM pro model: A sensor is placed in the clinic and worn for 14 days. The patient cannot see the readings to prevent them from acting on the blood glucose readings. 

CGMs for personal use consist of a sensor (to detect glucose values), a transmitter (to send blood glucose data), and a receiver (to display the data). Dr. Colburn notes that most people use their smartphone as a receiver and in newer models, the sensor and transmitter are combined. Dr. Colburn instructs patients to apply a sensor to the back of the upper arm while holding their arm parallel to the floor with the elbow flexed at 90 degrees.

The two common models of CGMs available in the United States, Dexcom and Freestyle, have sensors that can be worn for 10 days or 14 days respectively. Thus, prescribers should write for 2 or 3 sensors per month. The Dexcom G6 requires a transmitter, which has a 3 month battery life, but the Dexcom G7 has a transmitter built into the sensor “all-in-one“. For Dexcom patients should download the Dexcom app and sign up for the patient portal, Clarity. For Freestyle patients only need to download the app. Dr. Colburn and The Curbsiders do not have a preference or any personal interest in either brand.

Smartphones can upload blood glucose data to the cloud which can be monitored by the treating clinician, caregivers, or family members. Dr. Colburn notes that most practices set up a group account rather than individual accounts for each clinician to allow for cross-coverage. 

CGM Data

Below are standardized CGM metrics (Szmuilowicz, 2022)

• Time in range (TIR) is defined as glucose 70-180 mg/dL. The goal TIR is at least 70%. 
• Time above range (TAR) is defined as glucose above 180 mg/dL The goal TAR is under 30%.
• Time below range (TBR) is defined as glucose below 70 mg/dL. The goal TBR is under 5%.
• Graphs of the daily glucose trend are also provided. 

Dr. Colburn encourages patients to keep a record of eating behaviors and activity patterns to help make sense of glucose trends.  

A1C vs CGM Data

While the A1C gives a three-month look back, the TIR is more “real-time” since it provides a 10 to 14 day look back based on the most recent sensor data. Further, the A1C gives an average glucose, but it might miss wide variations in blood glucose readings captured by a CGM. Finally, CGM data is not affected by conditions like anemia, which can falsely raise or lower the A1C. 

On the contrary, CGM readings are susceptible to interference from certain substances. For instance, the earlier models of Dexcom were subject to interference from acetaminophen and the Dexcom G6 may have falsely elevated readings in patients taking hydroxyurea (Heinemann, 2022). The Freestyle device appears to be prone to interference by ascorbic acid (Heinemann, 2022). 

Dr. Colburn points out that CGMs have an alarm for lows and highs that can be set to customized values (e.g. under 70 mg/dL or above 250 mg/dL). He cautions that CGMs measure glucose in interstitial fluid (NOT in the blood), which is about 15 minutes behind the actual blood glucose value with current models (Zaharieva, 2019). This is of particular concern if a patient has blood sugar that is rapidly rising or falling and could cause a delay in the treatment of hypoglycemia.

How to Treat Common Blood Glucose Patterns

When evaluating blood glucose patterns, first, address any hypoglycemia and then, address hyperglycemia.

Broadly, metformin*, GLP1 agonists, SGLT2 inhibitors, and DPP4 inhibitors can lower both fasting and postprandial glucose (Szmuilowicz, 2022). These agents should not cause significant hypoglycemia in patients unless they are also taking insulin or an insulin secretagogue (i.e. sulfonylurea). 

*Metformin and basal insulin mainly target fasting blood glucose. 

Below are some common blood glucose patterns and some potential approaches to treatment. Remember that there is often more than one right answer in diabetes care.

Nocturnal Hypoglycemia

Nocturnal hypoglycemic events often wake patients due to counterregulatory hormones (glucagon, growth hormone, cortisol, epi/norepinephrine) changes aimed at blood glucose normalization. Dr. Colburn cautions that patients should not, “just let the body fix” their hypoglycemia because recurrent hypoglycemia can be damaging and has been associated with increased mortality, poor cognitive function (in children), and possibly dementia in adults (Amiel, 2021)! If hypoglycemia occurs, follow the rule of 15, take 15 grams of carbs, and repeat the blood glucose in 15 minutes. See Curbsiders episode #397 Insulin, T2DM, Fanny Packs, and Hypoglycemia. 

Reduce the dose of basal insulin for patients with nocturnal hypoglycemia. This change might paradoxically improve the A1C because as Dr. Colburn notes, patients can have reduced insulin sensitivity for nearly 24 hours after a hypoglycemic event (Heller, 1991; Lucidi, 2010). Further, patients often eat high-sugar foods to self-treat hypoglycemia. Thus, lowering the basal insulin dose and avoiding hypoglycemia might improve the A1C by maintaining insulin sensitivity and avoiding the need to treat with high-sugar foods.

Omit the evening dose for patients on a sulfonylurea who are experiencing nocturnal hypoglycemia. Patients on a long-acting sulfonylurea might need to reduce the dose or stop it altogether. Dr. Colburn often switches to another class of agent since sulfonylureas do not have added organ benefits outside of surrogate endpoints like the need for retinal photocoagulation or microalbuminuria (UKPDS, 1998; ADVANCE, 2008).

Exercise-induced Hypoglycemia 

Patients with type 1 diabetes and type 2 diabetes treated with insulin or insulin secretagogues are at risk for exercise-induced hypoglycemia (Younk, 2011; Cockcroft, 2020) due to impaired counterregulatory response to exercise mitigated by diabetes itself and medications (Younk, 2011). Further, insulin sensitivity improves for hours (maybe up to 72 hours) after exercise (Bird, 2017). Rather than discouraging exercise, Dr. Colburn suggested a few strategies to mitigate the risk of hypoglycemia including reducing the basal insulin dose, reducing the preceding prandial insulin dose, or taking a snack with complex carbohydrates, protein, and fat (e.g. half a banana and peanut butter) prior to exercise –expert opinion. 

Fasting hyperglycemia

For fasting hyperglycemia, Dr. Colburn recommends increasing metformin to the maximally tolerated dose or increasing the basal insulin dose. He notes that introducing a GLP1 agonist or SGLT2 inhibitor is mainly targeted at postprandial hyperglycemia, but might help with fasting blood glucose as well –expert opinion. 

Postprandial hyperglycemia

Patients using conventional fingersticks to check blood glucose often check before meals and miss episodes of postprandial hyperglycemia. As CGM use increases, patients and clinicians will likely be more aware of post-meal spikes in blood glucose. 

GLP1 agonists (including GIP/GLP1 agents), SGLT2 inhibitors, DPP4 inhibitors, or mealtime insulin can help with postprandial hyperglycemia.  As discussed with Dr. Colburn, adding a GLP1 agonist or SGLT2 inhibitor (or both) to basal insulin and/or metformin can prevent the need for multiple daily insulin injections. However, some patients may require mealtime insulin. In those cases, patients can start by taking short-acting insulin with the largest meal of the day rather than injecting insulin at each meal (Samson, 2023), the so-called “basal plus one” approach.

DPP4 inhibitors have a limited role due to weak effects on A1C, cost, and lack of added organ benefit (Dungan, 2023 UpToDate accessed 17 March 2024).  

Kashlak Pearl: Dr. Colburn cautions that rapid-acting insulin should not be given between meals to avoid “stacking” doses. Patients should be instructed to take insulin at the prescribed times (e.g. once-daily basal insulin and rapid-acting insulin three times daily with meals). Patients should work with the prescribing clinician to make adjustments based on blood glucose data.

Generalized Hyperglycemia

Dr. Colburn finds this to be the least challenging pattern since it’s clear that medication needs to be added or increased. However, don’t forget to address lifestyle modifications!

Kashlak Pearl: Basal insulin has a ceiling effect at about 0.5 units/kg/day so further increases have diminishing returns and lead to “overbasalization”. 

Signs of overbasalization and the need to intensify therapy beyond basal insulin include (Cowart, 2020): 

1. basal insulin dose >0.5 units/kg/day
2. ≥50 mg/dL decrease in bedtime to fasting glucose
3. post-meal glucose >180 mg/dL 
4. an A1C not at goal despite normal fasting blood glucose 

Dr. Colburn recommends addressing fasting glucose first and then, addressing mealtime needs. GLP1 agonists and SGLT2 inhibitors have added organ benefits so the choice between them can be dictated by a patient’s comorbid conditions (e.g. obesity, CKD, heart failure, etc.). Remember, while insulin helps lower blood glucose, it lacks added organ benefits in type 2 diabetes and puts the patient at risk for hypoglycemia and weight gain (ACCORD, 2008). That said, Dr. Colburn notes that clinical inertia often delays the initiation of insulin. Remember, you can always back off on insulin as glucose control improves, especially after the addition of adjuvant meds like GLP1 agonists and/or SGLT2 inhibitors. 

Links

1. Steven Saylor book series (historical fiction)

Goal

Listeners will learn how to recognize and respond to patterns observed in blood glucose readings

Learning objectives

After listening to this episode listeners will…

1. Recognize and respond to common patterns observed when reviewing blood glucose readings
2. Determine how and when to prescribe continuous glucose monitoring

Disclosures

Dr. Colburn has no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Watto MF, Colburn J, Emi Okamoto, Williams PN. “#433 CGMs, Insulin, and How to Adjust Diabetes Meds to Match Blood Glucose Patterns”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast Final publishing date April 1, 2024.