Pharmacodynamics
What a drug does once it arrives. Concentration is pharmacokinetics; the effect that follows, and how it changes over time, is pharmacodynamics.
Pharmacodynamics (PD) links the concentration of a drug at its target to the effect it produces. Where pharmacokinetics asks how much drug is in the blood, pharmacodynamics asks what that amount does: which receptors it activates, which effects follow, how big they are and whether they hold up over time.
Dose-response
Most effects rise with dose, then flatten. The flat part is the ceiling, sometimes written Emax; the dose giving half that maximum is the ED50 or, for concentration, the EC50. Past the steep part of the curve, a higher dose buys less extra effect and often more side effects.
SURMOUNT-1 shows a typical shape. Over 72 weeks, under the treatment-regimen estimand:
| Tirzepatide dose | Mean weight change at 72 weeks | Stopped for adverse events |
|---|---|---|
| Placebo | -3.1% | 2.6% |
| 5 mg | -15.0% | 4.3% |
| 10 mg | -19.5% | 7.1% |
| 15 mg | -20.9% | 6.2% |
Going from 5 to 10 mg added 4.5 points of weight loss. Going from 10 to 15 mg added 1.4. The curve was flattening. That is one reason the titration schedule and the choice of maintenance dose belong with the prescriber rather than with "more is better".
Effects that fade, and effects that do not
Not every effect of a drug follows the same time course. The Zepbound label states that tirzepatide delays gastric emptying, that "the delay is largest after the first dose and this effect diminishes over time". After a first 5 mg dose, the peak concentration of paracetamol given at the same time fell by 55 percent; at week 6 on 15 mg, there was no meaningful effect. The weight effect, by contrast, kept building for months. That split helps explain why nausea is worst in the first weeks of each dose step and then eases while weight loss continues.
Some effects persist for as long as the drug is taken. The Wegovy label reports mean resting heart rate increases of 1 to 4 beats per minute against placebo in the weight trials.
Glucose-dependent effects
The GLP-1 drugs stimulate insulin release and reduce glucagon in a glucose-dependent way, according to the Wegovy label. The effect is strong when glucose is high and weak when it is normal. That is a pharmacodynamic property, and it is why these drugs on their own rarely cause low blood sugar. The risk rises when they are combined with insulin or a sulfonylurea, which act regardless of glucose.
Why PD matters more than half-life
A drug can stay in the blood long after an effect has faded, or produce an effect that outlasts the drug. Half-life tells you about concentration. Only pharmacodynamic data, ideally from trials, tells you about effect. For most research peptides that data does not exist in people.
The dose log keeps dose, weight and side effects on one timeline, which is the personal version of a dose-response curve: what each step did for you, and when the side effects of a step faded.
Related terms: pharmacokinetics, receptor agonist, titration, half-life. Back to the glossary.
Questions people ask
What is pharmacodynamics?
What a drug does to the body once it reaches its target: the effects, their size, how they depend on dose and how they change over time.
Does a higher GLP-1 dose always mean more weight loss?
Usually more, but with diminishing returns. In SURMOUNT-1, tirzepatide 5, 10 and 15 mg gave -15.0, -19.5 and -20.9 percent at 72 weeks against -3.1 percent on placebo.
Why does nausea fade but weight loss continue?
Different effects have different time courses. The Zepbound label says the delay in gastric emptying is largest after the first dose and diminishes over time, while weight loss built over months.
Do GLP-1 drugs cause low blood sugar?
Rarely on their own, because their effect on insulin is glucose-dependent. The risk rises with insulin or a sulfonylurea.
Sources
- Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1), New England Journal of Medicine, 2022
- Zepbound prescribing information, Eli Lilly
- Wegovy prescribing information, Novo Nordisk
- Mechanisms of action and therapeutic application of glucagon-like peptide-1 (Drucker), Cell Metabolism, 2018
