Susan Brian MD

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2 weeks ago | [YT] | 7

Susan Brian MD

Important orforglipron (Foundayo) drug interaction with simvastatin (zocor) to know about

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2 weeks ago | [YT] | 9

Susan Brian MD

What does “microdosing” a GLP-1 actually mean?

A new real-world study published August 31, 2026, looked at patients who remained on the lowest doses of semaglutide or tirzepatide for at least 6 months.

The results are interesting—but they need to be interpreted carefully.

Among patients meeting the study’s definition of sustained low-dose treatment, tirzepatide was associated with greater weight loss than semaglutide:

12-month weight change: −5.5% with tirzepatide vs −2.2% with semaglutide.

There were also differences in reported adverse events. Several—including constipation and acute kidney injury—were more common in the tirzepatide group, while otitis, diaphoresis, and ankle swelling were more common with semaglutide.

!!this is where the study becomes particularly important to interpret correctly.

This was not a randomized trial of intentional “microdosing.” The investigators used prescription patterns as a real-world proxy for sustained treatment at the lowest dose.

Only 814 of 490,072 semaglutide-treated patients and 1,016 of 322,442 tirzepatide-treated patients met the stringent criteria for sustained low-dose treatment.

That tells us something important: staying on these doses for an extended period is relatively uncommon in routine prescribing.

Because this was an observational study, we also cannot assume that the differences were caused by the medications themselves. Patients who remain on low doses may differ from those who escalate doses for many reasons—including tolerability, access, cost, medication availability, treatment goals, or clinical characteristics.

So I would not interpret this study as evidence that everyone should remain on 0.25 mg semaglutide or 2.5 mg tirzepatide.

But I do think it raises an important clinical question:

Does every patient need to reach the highest studied maintenance dose to achieve meaningful benefit?

We often approach GLP-1 therapy with a dose-escalation paradigm: start low, increase gradually, and ultimately reach a recommended maintenance dose.

Real-world treatment is more individualized.

Some patients may achieve their desired degree of weight loss or metabolic improvement at a lower dose. Others may need substantially higher doses. And some may be limited by adverse effects.

The question is whether we can eventually identify the lowest effective dose for an individual patient, rather than assuming that one maintenance dose is optimal for everyone.

This study doesn’t answer that question.

But it provides an interesting rationale for prospective trials specifically designed to evaluate sustained lower-dose GLP-1 therapy.

In my view, that’s the next study we need—not more anecdotes about “microdosing,” but well-designed clinical trials that tell us who benefits, how much benefit they receive, and what the long-term safety profile looks like at lower doses.

Reference: Murugadoss K, Venkatakrishnan AJ, Soundararajan V. Comparison of Cardiometabolic Benefits and Tolerability in Patients on Sustained Low Doses of Semaglutide or Tirzepatide. Biology Methods and Protocols. 2026; bpag048. doi:10.1093/biomethods/bpag048.

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1 month ago | [YT] | 10

Susan Brian MD

Have you heard of Zenagamtide yet?

It has been called “amycretin” until now.

It’s an investigational dual GLP-1/amylin receptor agonist from Novo in research currently for obesity and type 2 diabetes.

It’s different than CagriSema (I think will likely be approved in 2027), which combines two separate drugs, zenagamtide is a single molecule designed to activate both pathways.

Early trials have shown significant weight loss— 24% at 36 weeks —although this was a small early-phase study (larger Phase 3 trials now underway)

It is also being developed as an oral medication.

The most common side effects so far are gastrointestinal, similar to other incretin-based drugs, and it is not yet FDA-approved

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1 month ago | [YT] | 10

Susan Brian MD

Sobel TH, Shen W. Menopause. 2022;29(4):483–490. doi:10.1097/GME.0000000000001938.

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1 month ago | [YT] | 3

Susan Brian MD

Insulin resistance is often talked about as if it has one clear symptom or a single blood test that can diagnose it, but it’s more complex than that.

Insulin resistance is a physiologic state where the body needs more insulin than normal to keep blood sugar in a healthy range. Because of this, a person can have insulin resistance for years before developing prediabetes or type 2 diabetes.

Certain physical and metabolic signs can raise suspicion, including acanthosis nigricans (darkened skin patches), increased abdominal fat, high blood pressure, high triglycerides, low HDL cholesterol, MASLD (fatty liver disease), and PCOS. However, none of these findings alone is enough to make a diagnosis.

In research and some clinical settings, insulin resistance can be estimated using HOMA-IR (Homeostatic Model Assessment of Insulin Resistance). This is calculated from fasting blood tests: fasting insulin (µU/mL) × fasting glucose (mg/dL) ÷ 405. In general, higher values suggest greater insulin resistance. However, there is no single agreed-upon cutoff that defines insulin resistance. Different studies use different thresholds, and values around 2.0–2.5 are sometimes used in research, but these should not be treated as a universal diagnostic standard.

HOMA-IR does correlate reasonably well with more precise methods, such as the glucose clamp technique, when looking at large groups of people. However, it is not commonly used in routine medical care to diagnose insulin resistance, mainly because insulin testing is not standardized across laboratories and there is no consistent clinical cutoff.

It’s also important to understand that the percentage of people labeled as having “elevated” HOMA-IR varies widely. It depends entirely on the cutoff used and the population being studied, so there is no single fixed prevalence.

Current guidelines, including the 2026 ADA Standards of Care, recommend using established tests such as A1C, fasting plasma glucose, or an oral glucose tolerance test to screen for prediabetes and type 2 diabetes, rather than relying on HOMA-IR.

Overall, the key message is that metabolic risk can be identified early. We do not need to wait for diabetes to develop before recognizing or addressing insulin resistance.

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1 month ago | [YT] | 0

Susan Brian MD

I’m pretty excited about the possibility of CagriSema getting FDA approval.

Did you see the new study?

The phase 3a REIMAGINE 3 trial was just published in The Lancet (July 2026)— it evaluated once-weekly cagrilintide–semaglutide (CagriSema) as an add-on to basal insulin in 274 adults with type 2 diabetes and lasted 40 weeks. (this medicine hasn’t been FDA approved yet)

The A1c reduction was very impressive!

Both the 2.4 mg and 1.0 mg doses produced substantially greater HbA1c reductions than placebo (−2.33% and −2.10% vs. −0.66%), while also helping with significant weight loss.

ALSO***What makes these findings really interesting is that these improvements were achieved without increasing the risk of hypoglycemia, despite participants remaining on basal insulin—a common concern whenever any medicine is added to insulin (we counsel our patients about lowering the insulin appropriately )

CagriSema looks like it might become a great option for people with type 2 diabetes on basal insulin but still struggling to reach glycemic and weight-management goals.

2 months ago | [YT] | 0

Susan Brian MD

Thanks to Dr Hollie Wakelyn, PharmD for her help with this chart - use it to help change between estrogen doses while there is a patch shortage!

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2 months ago | [YT] | 0

Susan Brian MD

I think you might have to tap on the image to see the full text? Let me know if you have any questions below!⬇️

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2 months ago | [YT] | 0