Pioneers in Karelia

PIONEER Studies Converge at the ADA Meeting

Some of the most discussed news coming from the American Diabetes Association Scientific Sessions in San Francisco is all about the PIONEER studies of oral semaglutide. This drug is presently under review at FDA for type 2 diabetes. Interest is keen because it will be the first of its class that doesn’t require an injection. One of the studies – PIONEER 4 – came out in Lancet simultaneously with its presentation at ADA yesterday.

Superior Weight Outcomes

PIONEER 4 was a 52-week study comparing oral semaglutide to injectable liraglutide and placebo. For lowering HbA1c, oral semaglutide was at least as good as liraglutide. But the reductions in weight were superior. On average, patients on semaglutide lost about nine pounds. On liraglutide, they lost seven.

Note that this is a study of doses for diabetes, not obesity. For both drugs, the optimal dose for obesity is higher. Nonetheless, these results line up with prior studies that lead many people to have high hopes for semaglutide as an advance for treating obesity. However that indication is likely to be at least two years away.

For type 2 diabetes, FDA approval of oral semaglutide could come as early as this fall.

Superiority versus Empagliflozin

The other study presented at ADA was the PIONEER 2 study. It compared oral semaglutide to empagliflozin. This study was also 52 weeks. Semaglutide had superior HbA1c outcomes at both 26 weeks and 52 weeks. Its weight outcomes were superior only after 52 weeks.

In both of these studies, the most common adverse effect for semaglutide was nausea. About 20 percent of patients reported it, though it generally faded with time. Adverse events led 11 percent of the patients on semaglutide to stop taking it. A bit less than half of those discontinuations were due to nausea.


Semaglutide is already available as a weekly injection and it’s doing quite well under the brand name Ozempic for type 2 diabetes. But in practical human terms, an oral form could be quite important to the people who need it. This will be the first ever oral GLP-1 agonist. A needle is simply something that many people will avoid at all costs.

We are hoping that this drug will fulfill the promise these data suggest. But only time will tell.

Click here for the study in Lancet and here for the abstract of the PIONEER 2 study. For additional reporting on these studies, click here.

Pioneers in Karelia, painting by Pekka Halonen / WikiArt

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June 9, 2019

One Response to “PIONEER Studies Converge at the ADA Meeting”

  1. June 09, 2019 at 8:23 am, David Brown said:

    Question: Do we know what causes type 2 diabetes and how to prevent it? The answer is yes. However, the focus on treatment, rather than prevention, has clouded the understanding of the scientists who control the narrative. The linoleic acid debate is a prime example of scientists drawing conclusions while ignoring the need for a biologically plausible explanation. While research demonstrates unequivocally that high linoleic acid intake has benefits for controlling blood sugar,[1] there is other, better quality research that shows greater benefit with lowered linoleic acid intake.[2]

    Here is what the pro-high linoleic acid faction concludes. “Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.”[3]

    On the other hand; “Confusingly, assays of n-6 status in pathological tissues often show a lower level of n-6 than other fatty acids, and in these cases, addition of n-6 can actually improve function. This appears to be due to the chain reaction depleting LA or arachidonic acid (AA). The latter is a long-chain n-6 fatty acid produced in the body from LA. N-6 levels are lower, but HNE levels have risen as N-6 is converted into OxLAMs.[2]

    Norwegian animal science researcher Anna Haug seems to have a biologically plausible explanation as to why the Mediterranean style diet furnishes such favorable results. Typically, arachidonic acid intake is reduced because of lower meat intake. Linoleic acid intake is lower due to emphasis on using olive oil in place of linoleic acid-rich seed oils. Here’s what she says. “Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet…Chicken meat is commonly regarded as a healthy type of meat; it is popular, and hence the consumption has increased. Chicken meat is lean, protein-rich and rich also in other important nutrients. However, the fatty acid composition is strongly dependent on the diet fed to the birds. A typical modern poultry diet is rich in cereals having a high ratio between omega-6 and omega-3 fatty acids. This diet is very different from the natural diet for the same species containing more green leaves that are rich in the omega-3 fatty acid alpha-linolenic acid (ALA)…Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid… High rates of production of these mutagenic aldehydes must be expected simultaneously to lead to enhancement of the risk of various forms of cancer, and enhancement of the rate of mitochondrial DNA aging, which could lead to earlier onset of various age-associated degenerative diseases perhaps including type 2 diabetes. The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span.[4]

    In the final analysis, the food supply is defective due to the practice of feeding grain to livestock. Sprouted grain would be OK because the linoleic acid gets converted to something beneficial in the germination process.[5]