392 - Semaglutide for Weight Loss, Continuous Glucose Monitors

From the Literature

1) Once Weekly Semaglutide for Weight Loss

The search for effective and non-toxic weight loss medications continues. Liraglutide (Saxenda, Victoza) is already approved for daily injections for obesity (in addition to its diabetes indication). Semaglutide (Ozempic) could be an easier, once-weekly injection to accomplish the same goal. In this study, over nineteen hundred subjects who were obese (Body Mass Index (BMI) >=40, or >= 35 with comorbidities) were enrolled and given weekly lifestyle counseling plus semaglutide or matching placebo. The lifestyle recommendations were straightforward – reduce calories by 500 kcal/day and get the recommended 150 minutes of moderate-vigorous exercise per week. Semaglutide was started at 0.25 mg per week, and increased to a goal of 2.4 mg/wk. The trial was well-designed overall.

About 40% of the subjects had “prediabetes”, their mean weight was ~ 230 lb., about ¾ of them were female, 88% were white or Asian, and their mean BMI was around 38. The groups were well-balanced.

In the intention-to-treat analyses after 68 weeks (1 year, 4 months), the weekly semaglutide resulted in a 12% reduction in body weight on average (about 27 pounds for a 230 pound person).

Many secondary cardiometabolic outcomes (BP, lipids, glucose, etc.) improved also. More subjects in the semaglutide group achieved and sustained 5% (55% more), 10% (57% more) and 15% (45% more) weight loss thresholds than those taking placebo. Adverse events were common (89.7% with semaglutide vs. 86.4% with placebo, NNH = 33), but most of these were mild – GI effects and injection/allergy reactions. Serious adverse events occurred in 9.8% of semaglutide participants vs. 6.4% with placebo, NNH = 33, with the difference attributed to serious GI and hepatobiliary issues. Pancreatitis happened in 3 semaglutide subjects, but one had a previous history, and the other two had coincident gallstones.

John’s Comments:

Before we all rush for semaglutide in treating obesity, we should see this study as encouraging but not convincing. Twenty-seven pounds over 68 weeks is less than ½ pound per week – a rate that will frustrate those looking for short-term success. The subjects were also a fairly specific group – white females with a lot of prediabetes. This is a promising line of research that is showing consistent benefits, so I have some hope.

Of note, among the subgroup with prediabetes, while 84% in the semaglutide group became normoglycemic (which is great…), 48% also did in the placebo group (who, as you recall, received relatively simple lifestyle advice). Is that the power of simple dietary advice or an example of the strength of a placebo that hurts a little? My hope is the former.

Reference:

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. Published online February 10, 2021: Link

From the Literature and Clinical Experience

2)  Continuous Glucose Monitors (CGM) – Pros, Cons, and More

In the February 1^st Take 3, we reviewed the 2021 ADA Standards of Care for Diabetes. The standards include the following recommendations for the use of CGM:

• Although self-monitoring of blood glucose in patients on noninsulin therapies has not shown clinically significant reductions in A1C, it may be helpful when altering diet, physical activity, and/or medications (particularly medications that can cause hypoglycemia) in conjunction with a treatment adjustment program. E
• CGM serves an important role in assessing the effectiveness and safety of treatment in patients with T2D on intensive insulin regimens and with hypoglycemia. 
• When used properly, real-time and intermittently scanned CGM in conjunction with insulin therapy are useful tools to lower A1C and/or reduce hypoglycemia in adults with T2D who are not meeting glycemic targets. B
• Data from CGM allows providers to analyze new metrics for glycemic targets. These metrics include average blood glucose, percentage of time in range (TIR: 70–180), glycemic variability, and percentage of time spent above and below range.
• TIR is associated with the risk of microvascular complications and can be used for assessment of glycemic control. Additionally, time below target (<70 and <54) and time above target (>180) are useful parameters for reevaluation of a regimen. C
• If using Ambulatory Glucose Profile (AGP) report/Glucose Management Indicator (GMI) to assess glycemia, a goal is a TIR of >70% with time below range <4%. B
• In patients on a multiple daily injection (MDI) regimen, real-time CGM devices should be used as close to daily as possible for maximal benefit. A Intermittently scanned CGM devices should be scanned frequently, at a minimum once every 8 hours.

Since these devices are being advertised and promoted aggressively to patients and appear quite “trendy, below are some “pros/cons” of these devices as well as other important information on the literature and clinical experience:

Pros:

• When used properly, CGMs can be used in conjunction with insulin therapy to improve hemoglobin A1c and reduce hypoglycemic events
• Real-time glucose alarms can alert the patient when their blood glucose levels are above or below a certain threshold, allowing the patient the opportunity to correct
• Patients with frequent hypoglycemia or hypoglycemia unawareness can have life-saving alerts which can prevent coma, seizure, arrhythmia, and/or death
• Some CGMs can communicate with insulin pumps and can adjust basal and/bolus dosing
• Trends in data can allow for more specific dosage adjustments
• Patient and provider can see how different foods or activities affect the patient’s glucose levels
• Remote monitoring with some CGMs (e.g Dexcom G6) can allow caregivers to follow along

Cons

• Requires extensive diabetes education and training in order to use CGM optimally
• Some CGMs may still require multiple daily calibrations, requiring multiple daily finger sticks (e.g. Medtronic Guardian)
• Some CGMs still require the patient to intermittently scan their device, checking their blood glucose levels every 8 hours. If the patient is unable to do this or forgets, glucose data can be lost (e.g. Freestyle Libre 14 day)
• Depending on the patient’s insurance, they may have to meet criteria to qualify for a CGM. Devices can be very expensive if you must pay out of pocket. Obtaining devices through DME companies can be challenging

Coverage information for Continuous Glucose Monitoring Systems

• Commercial Insurance Requirements: If patient’s fill their CGM prescription at any major retail pharmacy, then:No criteria to be met
  • No Prior Authorizations Required
  • Cost <$75 for Reader (one-time purchase)
  • Cost <$75 for Sensors (purchase 2 every month)
  • If asked to pay >$75, patient can call Abbott (FreeStyle Libre): 844-330-5535 to request payment voucher that brings cost to <$75.

• Medicare Coverage Requirements:
  • Patient’s must obtain CGM (of any type) through DME. Each plan has preferred DME.
  • Patient has Type 1 or Type 2 Diabetes
  • Patient must be testing at least 4x/day and testing is documented clearly in the patient’s chart
  • Patient must be injecting insulin at least 3x/day and requires frequent adjustments
  • Patient has been seen by physician in at least the last 6 months
  • Documentation for medical necessity for patient to have therapeutic CGM is necessary. Sample statement of medical necessity: “CGM will allow us to remotely monitor patient's glucose levels and will help us make any necessary adjustments to their diabetes regimen, while keeping our patients safe and staff informed”
  • Patients should expect a call from DME to review copay
  • Copay based on patient’s individual plan. No copay assistance for patients with Medicare

• Medicaid Coverage Requirements:
  • Coverage Requirements are the same as Medicare
  • In Virginia, all plans with the exception of VA Premiere must obtain CGM (of any type) through DME and a prior authorization is required. Each plan has a preferred DME. For readers outside of Virginia, refer to your state Medicaid plans.
  • VA Premiere has Freestyle Libre 2 as preferred status. No PA or criteria are required. Can be received from any major retail pharmacy
  • Copays range from $0-$10 for the reader and sensors

Billing Codes that can be used with Continuous Glucose Monitors

• Professional CGM: 95250 (e.g., sensor placement, hook-up, calibration, patient training, sensor removal, download)
  • Can be completed by a healthcare professional under the direct supervision of a physician, physician assistant, or nurse practitioner. Modifier 52 should be used if the monitoring was for a duration of less than 72 hours.
• Personal CGM: 95249 (e.g., sensor placement, hook-up, calibration, patient training, sensor removal)
  • Can be completed by a healthcare professional under the direct supervision of a physician, physician assistant, or nurse practitioner.
• Interpretation of CGM data: 95251 (personal or professional use)
  • Physician, physician assistant, or nurse practitioner must be involved (e.g., direct involvement, co-signature) in order comply with Medicare requirements.
  • Can only be used one time/month per patient.

Mark’s Comments:

Many thanks to Carilion Family Medicine Faculty colleague Randi Earls, PharmD, CDCES as well as Aaron Estep, DO, Carilion PGY-2 Family Medicine Resident, for taking the lead on writing this Pointer.

While I appreciate how this technology can help support improved blood sugar awareness, remember that a CGM in and of itself will not lower anyone’s blood sugar. For some patients it may help to motivate the changes that could, including lifestyle changes, medication adherence, and medication adjustment for those with poor control. Therefore, CGMs should only be used in the context of a comprehensive plan for blood sugar management and close follow-up to monitor those changes in appropriately motivated patients, preferably for those using insulin. And remember, for those patients with DM and a BMI > 35 (and certainly >40) who have been unable to lose weight despite lifestyle counseling, consider a Bariatric Medicine referral if such resources are available in your area.

References:

• ADA Standards of Care 2021: January 1, 2021; 44(S1). Link
• Pharmacist’s Letter: Continuous Glucose Monitors FAQs (by subscription). February 2018.
• ADA CGM: Safe at School Guidelines: Link
• American Diabetes Association: Choosing a CGM: Link

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Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org