Two-Thirds of Your Pill Is Not the Drug | The Angry Gut, Chapter 2

Deprescribing · baseline measurement

Deprescribing Starts With a Baseline, Not a Drug List

Deprescribing should start from a current baseline measurement, not the drug list alone, because the list holds no record of whether the physiology each drug was started for has moved. Measura supplies those measurements; the ordering physician owns every deprescribing decision.

A medication review checks what a patient takes. It rarely checks whether the reasons each drug was started are still true, and that second question needs a measurement.

Deprescribing is usually organized around the drug list: interactions, duplications, criteria for older adults. The list is the wrong unit of analysis for two reasons. It omits the formulation chemistry that makes up most of each tablet’s mass, and it holds no record of whether the physiology each drug was started for has moved. A multi-drug patient reviewed without a current measurement is being deprescribed on memory.

Chapter 2 of The Angry Gut, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes, shown on camera as Two-Thirds of Your Pill Is Not the Drug, builds its argument around a single sixty-eight-year-old on nine prescriptions. Measura [Cardiometabolic and Autonomic Health Analysis] does not audit medications or advise on them. It supplies measurements to the ordering physician, who owns every decision. The sections below cover where those measurements fit a deprescribing workflow and where they do not.

Who should be considered for deprescribing?

The population is large. In one analysis of US prescribing, 39.0% of adults over 65 took at least five prescription medications daily, and a patient on 10 prescriptions ingests an average of 2.8 g of inactive ingredients per day. The index case will be familiar to primary care, pain and geriatric clinicians: a statin, an antihypertensive, metformin, a proton pump inhibitor renewed for eleven years, a daily NSAID, low-dose aspirin, an antidepressant, a laxative and a multivitamin, with bloating, alternating bowel habit and fatigue attributed to age.

Three features should flag the chart. A daily agent whose indication has not been revisited in years. A gastrointestinal symptom managed with another prescription. A symptom attributed to age with no measurement behind the attribution. In the index bag, the laxative was treating what the other eight bottles produced. Those features can be written into selection criteria instead of being left to recall.

What is in a pill besides the drug?

By mass, the most prescribed US oral medications are about 75% inactive ingredient, and 92.8% of oral solids contain at least one potential allergen. Only 28% of active ingredients have a formulation that avoids all of them. The substitution space is still wide: the 18 most prescribed oral drugs average 82.5 alternative formulations per active ingredient, and levothyroxine exists in 140 formulations made by 43 manufacturers. For many patients the actionable move is reformulation rather than discontinuation.

The exposure that matters for the gut is luminal, not systemic. Excipients that never reach meaningful plasma concentrations can sit at hundreds of micromolar to millimolar inside the gastrointestinal tract. Titanium dioxide is the worked example. In rats fed food-grade particles at dietary levels for 100 days, colonic TNF-α rose 26% and IL-8 rose 45%, with no change in paracellular permeability: immune disturbance supported, barrier failure in a healthy animal not shown. Europe removed it from food and kept it in medicines on supply grounds. In the book’s terms, the first brain, the gut, absorbs that exposure at full concentration; the second brain in the skull barely registers it.

Measura does not measure excipient exposure. It is read from the product record by the prescriber and pharmacist.

Can daily NSAIDs injure the small bowel without anyone noticing?

NSAID enteropathy is the injury least likely to reach a problem list. In 40 healthy volunteers given two weeks of a standard NSAID dose, capsule enteroscopy found new pathology in 68% and mucosal breaks in 40%, and fecal calprotectin rose above normal in 75%. In an unselected health-check cohort, aspirin users had small-bowel mucosal breaks at 36.9% against 6.3%, an odds ratio of 6.17. Co-prescribed acid suppression did not protect the small bowel; injury was 2.7 times more frequent with celecoxib plus rabeprazole than with celecoxib plus placebo. The one agent with a healing signal, misoprostol, achieved complete healing in 28.6% against 9.5%.

The counterevidence deserves its tier. A 2026 randomized trial found indomethacin did not raise mannitol-based permeability in healthy volunteers, yet symptom scores rose from 15.5 to 17.3 with an interval excluding zero. The cohort was healthy, dosing lasted six days, and the placebo arms were small. The practice’s position is that the camera findings govern the older multi-drug patient such trials exclude. Capsule endoscopy and calprotectin are gastrointestinal studies performed elsewhere and are not part of the Measura library.

Can medications change the gut microbiome?

Polypharmacy leaves reproducible microbial fingerprints. Across 1,883 human fecal metagenomes, 19 of 41 drugs associated with microbial features; after correcting for concurrent use, the signal contracted to 47 associations involving six drugs, and no drug altered richness. In 4,198 people sampled twice, polypharmacy-related community structures shifted with drug initiation and recovered with cessation. A depletion once proposed as a microbial marker of major depression was explained, in 1,802 people, by SSRI/SNRI status. Any microbiome result in a medicated patient has to be read against the bag. Measura does not run stool or microbiome testing.

What does a baseline measurement add to deprescribing?

The audit question with the most clinical weight is whether each indication still holds, and that is a measurement question. Measura contributes to the terrain side of it, not to drug toxicity:

Laboratory panels re-establish the metabolic state the metformin and statin were started for and give a dated baseline before any taper or substitution.
Arterial stiffness and endothelial function testing adds a direct vascular measurement alongside office blood pressure for patients on antihypertensive and lipid therapy.
Bioimpedance body composition matters because the enteropathy data are not only about drugs. In the same health-check cohort, obesity carried an odds ratio of 2.30 (1.38 to 3.92) for small-bowel breaks and smoking 1.85. Adiposity is a modifiable driver of metaflammation that a medication review never records.
Indirect calorimetry replaces an estimated resting energy expenditure with a measured one when fatigue has been attributed to age.

Findings change management in concrete ways. A metabolic panel that has normalized reopens the indication discussion for a drug started years earlier. A body-composition result moves weight and tobacco into the same plan as the medication changes. A documented baseline makes it possible to tell, after a reformulation, whether anything moved. Reading guidance sits in interpreting the report.

Building it into the visit

The multi-drug older adult is commonly seen at an annual wellness visit, which many practices already use for a medication review. Attaching a standing measurement protocol to that review keeps it reproducible instead of dependent on whichever clinician has time. Standing orders can define the trigger, such as a daily-medication count, a pharmacologically managed gastrointestinal symptom, or unexplained fatigue, and annual wellness visit integration covers where results land in the encounter. Practices running cognitive assessment and fall prevention pathways can add metabolic and body-composition measurement to the same visit, and the record of what was measured and acted on supports MIPS quality reporting.

Every study summarized here, with its limits and the results that argue the other way, is in the Deep Dive companion. The next chapter moves from the bag to the nerve that reports on it, covered for clinicians in why the LF/HF ratio is not vagal tone.

Frequently asked questions

What does deprescribing mean?

Deprescribing is the planned review of a patient’s medications to decide which can be reduced, substituted, reformulated or stopped. It is usually organized around the drug list: interactions, duplications and criteria for older adults. The list alone does not show whether the reason each drug was started still holds, so a current baseline measurement belongs in the review. The ordering physician owns every deprescribing decision.

Which patients should be measured before a deprescribing review?

Prioritize older adults on several daily agents, especially when a gastrointestinal symptom is being managed with another drug or fatigue has been attributed to age without a workup. In one US analysis, 39.0% of adults over 65 took at least five prescriptions daily, so a written trigger works better than clinician recall. See standing orders: making screening reproducible.

Does Measura detect NSAID enteropathy or excipient intolerance?

No. Small-bowel injury needs capsule endoscopy or related gastrointestinal studies, and excipient questions are answered from the product record. Measura measures the metabolic, vascular, body-composition and autonomic terrain of the same patient, which informs whether each indication still holds and gives a baseline for judging any change. See clinical rationale.

How should a negative permeability trial be weighed against capsule findings?

As a result in a different population. The 2026 indomethacin trial enrolled healthy volunteers for six days with small placebo arms, and symptom scores still rose. Capsule studies found mucosal breaks in 40% of healthy volunteers after two weeks and visible injury in 71% of chronic users. The older multi-drug patient resembles neither trial cohort closely. See specialty applications.

Can a microbiome result be interpreted in a patient on many drugs?

Only against the medication list. Proton pump inhibitors, metformin, antibiotics and laxatives showed the strongest associations in human cohorts, and a microbial signal once linked to depression turned out to track antidepressant use in 1,802 people. A result read without the bag risks labeling a prescription as a disease. See physician questions.

How should measurement be documented for quality programs?

Record the trigger, the measurements obtained, the dated values and the management decision each one informed, including a decision to continue a drug. That record supports value-based and quality programs as documentation of what was measured and acted on, without implying that a measurement replaced clinical judgment. See HEDIS and value-based care.

Measure the indication before revisiting it

Learn how the Measura protocol adds metabolic, vascular and body-composition baselines to a practice’s medication review and annual wellness workflow.

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